Belimumab Research Articles

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.

Belimumab (BEL) Improves Renal Outcomes in Active Lupus Nephritis (LN): A Phase 3 Randomized, Placebo (PBO)-Controlled Trial

Belimumab (BEL) Improves Renal Outcomes in Active Lupus Nephritis (LN): A Phase 3 Randomized, Placebo (PBO)-Controlled Trial

Immunogenicity, Tolerability, and Clinical Effectiveness of 23-Valent Polysaccharide Pneumococcal Vaccine in Patients with Systemic Lupus Erythematosus

The aim of the work is to study the immunogenicity, tolerability, and clinical efficacy of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE). Material and methods. The study included 61 patients with a confirmed diagnosis of SLE, including 53 women, 8 men, aged 19 to 68 years. The disease activity at the time of vaccination: in 9 patients — high, in 13 — medium, in 34 — low, in 5 — remission. Therapy outline: 59 patients received glucocorticoids (GC) 5–30 mg/day in terms of prednisolone, 45 — hydroxychloroquine (GC), 33 — cytostatics (CS), 22 — genetically engineered biological drugs (GEBD): 11 — rituximab (RTM), 10 — belimumab (BLM). 23-valent polysaccharide pneumococcal vaccine in an amount of 0.5 ml (1 dose) was injected subcutaneously. Follow-up period: 9 patients — 3 months, 52 — 1 year after the vaccination. Patients were examined before vaccination, as well as in 1, 3, and 12 months after the vaccination. Results and discussion. After a year of observation, the number of «responders» to vaccination was 61.5%, «non-responders» — 38.5%. There was a decreased response to vaccine in patients receiving GEBD compared with patients who did not receive GEBD (40% and 75%, respectively), p=0.02. No differences were found against the background of RTM and BLM therapy. Administering GC in a dose exceeding 10 mg/day did not lead to a more significant decrease in response to vaccine compared to other patients. Standard local vaccination reactions of mild to moderate severity were noted in 50.8% of the patients, general reaction of mild severity — in 1 patient (1.6%), hyperergic Arthus-like reaction — in 1 patient (1.6%), the symptoms of which were relieved in 7 days. During the observation period (1 year), not a single case of exacerbation of SLE, reliably associated with the vaccination, was registered, and no new autoimmune phenomena were identified. Clinically positive dynamics was noted in the form of a decrease in the number of episodes of pneumonia, as well as acute and exacerbated chronic bronchitis, sinusitis. Conclusion. Sufficient immunogenicity, good tolerance, and clinical effectiveness of PPV-23 in patients with SLE, incl. those, who received combined immunosuppressive therapy. Further studies are needed in large groups of patients with long follow-up periods.

OP0164 BLISS-LN: A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 TRIAL OF INTRAVENOUS BELIMUMAB IN PATIENTS WITH ACTIVE LUPUS NEPHRITIS

Background:Lupus nephritis (LN), a serious manifestation of systemic lupus erythematosus (SLE), affects nearly 70% of patients (pts) in high-risk groups. To preserve renal function, LN requires fast and effective treatment. Despite medical advances, progression rates at 15 years to end-stage renal disease (ESRD) remain >40% for pts with diffuse proliferative LN. Belimumab (BEL), approved in pts aged ≥5 years with active SLE, improved renal parameters in pts with baseline renal involvement in apost hocanalysis of Phase 3 trials data.Objectives:To assess efficacy and safety of intravenous (IV) BEL vs placebo (PBO), plus standard therapy (ST), in pts with active LN.Methods:BLISS-LN is a Phase 3, randomised, double-blind, PBO-controlled, 104-week study (GSK Study BEL114054,NCT01639339). Adults with SLE and biopsy-proven LN (class III, IV, and/or V) were randomised (1:1) to monthly BEL 10 mg/kg IV or PBO, plus ST. Primary endpoint: Primary Efficacy Renal Response (PERR); defined as urine protein creatinine ratio [uPCR] ≤0.7; estimated glomerular filtration rate [eGFR] within 20% of the pre-flare value or ≥60 ml/min/1.73m2; no rescue therapy) at Week (Wk) 104. Key secondary endpoints: Complete Renal Response (CRR; defined as uPCR <0.5; eGFR within 10% of the pre-flare value or ≥90 ml/min/1.73m2; no rescue therapy) at Wk 104; PERR at Wk 52; time to renal-related event (defined as ESRD/doubling of serum creatinine/renal worsening/renal disease-related treatment failure) or death. Other endpoints: time to PERR/CRR sustained through Wk 104; SLEDAI-S2K score <4 points at Wk 104; safety.Results:Overall, 448 pts were randomised (efficacy: 223/group; safety: 224/group). Significantly more BEL (43%) than PBO (32.3%) pts achieved PERR at Wk 104 (OR 1.55, 95% CI 1.04, 2.32; p=0.0311). More BEL than PBO pts achieved key secondary and other efficacy endpoints (Table).Overall, 214 (95.5%) BEL and 211 (94.2%) PBO pts had ≥1 adverse event (AE); 58 (25.9%) BEL and 67 (29.9%) PBO pts had ≥1 serious AE; 29 (12.9%) pts in each group had ≥1 AE resulting in study treatment discontinuation; 4 (1.8%) BEL and 3 (1.3%) PBO pts developed on-treatment fatal AEs.Conclusion:In the largest LN study to date, data from BLISS-LN demonstrate that BEL plus ST significantly improves LN renal responses compared with ST alone with a favourable safety profile.Study funding: GSK.Table.Endpoint, n (%)PBO(n=223)BEL(n=223)OR/HR (95% CI) vs PBOp-valueCRR at Wk 104*44 (19.7)67 (30.0)OR 1.74(1.11, 2.74)0.0167PERR at Wk 52*79 (35.4)104 (46.6)OR 1.59(1.06, 2.38)0.0245Time to PERR throughWk 104†72 (32.3)96 (43.0)HR 1.46(1.07, 1.98)0.0157Time to CRR throughWk 104†44 (19.7)67 (30.0)HR 1.58(1.08, 2.31)0.0189Time to renal-related event or death†63 (28.3)35 (15.7)HR 0.51(0.34, 0.77)0.0014SLEDAI-S2K score <4 points at Wk 104*41 (18.4)62 (27.8)OR 1.76(1.11, 2.78)0.0164*PBO and BEL columns represent the n (%) responders†Data presented as n (cumulative incidence)Disclosure of Interests:Richard Furie Grant/research support from: GSK, Consultant of: GSK, Brad H Rovin Grant/research support from: GSK, Consultant of: GSK, Frederic Houssiau Grant/research support from: UCB, Consultant of: GSK, Zahir Amoura Grant/research support from: GSK, Roche, Consultant of: GSK, Astra Zeneca, Amgen, Mittermayer Santiago: None declared, Gabriel Contreras Grant/research support from: Genentech, Merck, Consultant of: Genentech, Merck, Ana Malvar Consultant of: GSK and Roche, chi chiu mok: None declared, Amit Saxena Consultant of: GSK, AZ, BMS, Xueqing Yu: None declared, Y.K. Onno Teng Grant/research support from: GSK, Consultant of: GSK, Aurinia Pharmaceuticals, Novartis, Carly Barnett Shareholder of: GSK, Employee of: GSK, Susan Burriss Shareholder of: GSK, Employee of: GSK, Yulia Green Shareholder of: GSK, Employee of: GSK, Beulah Ji Shareholder of: GSK, Employee of: GSK, Christi Kleoudis Shareholder of: GSK, Consultant of: GSK, Employee of: Parexel, David Roth Shareholder of: GSK, Employee of: GSK

Clinical Efficacy of Routinely Administered Belimumab on Proteinuria and Neuropsychiatric Lupus.

Background and Objectives: Belimumab (BEL) is a monoclonal antibody approved for the treatment of active systemic lupus erythematosus (SLE) but not for lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE). We aimed to assess BEL's effects on these severe, potentially life-threatening manifestations.Methods: Retrospective observational cohort study using routine clinical data in a case series of patients with SLE receiving BEL.Results: Sixteen patients received BEL therapy for active SLE. Nine were excluded because they had no LN or NPSLE. Six suffered from LN, and one patient had NPSLE. All LN patients received BEL in addition to standard therapy including glucocorticoids, hydroxychloroquine, and mycophenolate mofetil in five cases, and tacrolimus in one case. Three patients with proteinuria >1,000 mg/g creatinine responded well (one complete, two partial renal responses); all other patients had decreasing proteinuria and a reduction in anti-dsDNA levels. The patient with NPSLE who had failed previous therapies had persistent clinical improvement of cutaneous and neuropsychiatric manifestations. There was one mild allergic reaction and one lower respiratory tract infection, but no other adverse events. One patient discontinued therapy due to a lack of improvement in clinical symptoms, another because of clinical remission.Conclusions: In our series, BEL led to a decrease of proteinuria in patients with proteinuria of more than 1,000 mg/g creatinine despite standard of care treatment, and led to a marked clinical improvement in one patient with NPSLE. No adverse events were observed. Routinely administered BEL shows clinical efficacy on non-approved manifestations, but careful patient selection is warranted.

A reverse translational study on the effect of rituximab, rituximab plus belimumab, or bortezomib on the humoral autoimmune response in SLE

ObjectivesSLE is a severe autoimmune disease characterized by autoreactive B cells and IC formation, which causes systemic inflammation. B cell–targeted therapy could be a promising treatment strategy in SLE patients; nevertheless, randomized clinical trials have not always been successful. However, some groups have demonstrated beneficial effects in severe SLE patients with off-label rituximab (RTX) with belimumab (BLM), or bortezomib (BTZ), which targeted different B cells subsets. This study assembled sera from SLE cohorts treated with RTX+BLM (n = 15), BTZ (n = 11) and RTX (n = 16) to get an in-depth insight into the immunological effects of these therapies on autoantibodies and IC formation.MethodsAutoantibodies relevant for IC formation and the avidity of anti-dsDNA were determined by ELISA. IC-mediated inflammation was studied by complement levels and ex vivo serum-induced neutrophil extracellular trap formation.ResultsReductions in autoantibodies were observed after all approaches, but the spectrum differed depending upon the treatment. Specifically, only RTX+BLM significantly decreased anti-C1q. Achieving seronegativity of ≥1 autoantibody, specifically anti-C1q, was associated with lower disease activity. In all SLE patients, the majority of anti-dsDNA autoantibodies had low avidity. RTX+BLM significantly reduced low-, medium- and high-avidity anti-dsDNA, while RTX and BTZ only significantly reduced medium avidity. IC-mediated inflammation, measured by C3 levels and neutrophil extracellular trap formation, improved after RTX+BLM and RTX but less after BTZ.ConclusionThis study demonstrated the impact of different B cell–targeted strategies on autoantibodies and IC formation and their potential clinical relevance in SLE.

PMDA investigations for vonoprazan, belimumab medicines

PMDA investigations for vonoprazan, belimumab medicines

Prospects for anti-BLyS treatment of systemic lupus erythematosus

Review of literature on the analysis of current data on the efficacy of belimumab (BLM) in systemic lupus erythematosus (SLE). It provides data on the high efficacy of BLM in high and medium activity of SLE in patients with joints damage, skin lesions and high immunological activity. The paper describes clinical cases of a rituximab and belimumab combination therapy in SLE patients.

Effect of biological agents on B-lymphocyte subpopulations in patients with systemic lupus erythematosus

Objective : to evaluate the effect of different biological agents (BAs), including rituximab (RTM) and belimumab (BLM) combination therapy, on B-lymphocyte subpopulations during a follow-up of patients with systemic lupus erythematosus (SLE). Patients and methods . The investigation enrolled 64 patients with a verified diagnosis of SLE with high and moderate disease activities according to the Systemic Lupus Erythromatosus Disease Activity Index (SLEDAI)-2K scores; 47patients of them took RTM, 10 used BLM, and 7 received RTM + BLM combination therapy. Peripheral blood B-lymphocyte subpopulations were measured by multicolor flow cytofluorom-etry, using a panel of monoclonal antibodies to B-lymphocyte surface membrane markers. The results were assessed using the SLEDAI-2K scores and the British Isles Lupus Assessment Group (BILAG) index. Results and discussion . RTM therapy led to a marked decrease in major B-lymphocyte populations, the residual cells being naXve B-cells and different memory B cell populations, the percentage of which depended on the degree of depletion after a RTM cycle. Incomplete B-lymphocyte depletion was associated with the large baseline numbers of plasma cells (PCs) (>0.2%). One year after initiation of therapy, the percentage ratio of B-lymphocyte subpopulations returned almost completely to baseline values, except the whole memory B-cellpopulation. BLM therapy resulted in a decrease in PCs and plasmablasts (PBs) to the point of their complete depletion. There were reductions in total CD19+ B-lym-phocytes and naive B lymphocytes. The use of the combination of BAs permitted the monitoring of the total B-lymphocyte population; its slower recovery was seen in patients with its complete depletion after a rituximab cycle. The therapy promoted maintenance of low concentrations of PCs and PBs, total memory B-cell and naive B-cell populations. Conclusion. In patients with SLE, all the three therapy with BAs demonstrated a good efficiency manifested by a decrease in clinical and laboratory disease activity. The found time course of changes in B-lymphocyte subpopulations can be used for the selection of therapy and for the evaluation of its efficacy.

THE EFFICIENCY OF BIOLOGICAL THERAPY AND THE FEATURES OF HUMORAL IMMUNITY IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Objective: to investigate the effect of various biological agents (BAs), including combined treatment with rituximab (RTM) and belimumab (BLM), on the activity of systemic lupus erythematosus (SLE) and to evaluate their efficacy and impact on some parameters of humoral immunity.Subjects and methods. BAs were prescribed to 54 patients with a reliable diagnosis of SLE with high and medium activity according to SLEDAI-2K; 40 of them received RTM, 7 – BLM; 7 – combined therapy with RTM and BLM. Clinical and laboratory examinations were made in all the patients at the time of their inclusion and then every 3 months during a year. The results were assessed using SLEDAI-2K, BILAG index, Lupus Erythematosus National Assessment (SELENA)-SLEDAI Flare index (SFI) (a moderate, severe exacerbation), and SLE Responder Index (SRI).Results and discussion. At 3, 6, and 12 months after start of therapy, the use of BAs in all the patients resulted in a disease activity reduction. It was statistically significant (p < 0.00001) in the RTM group; and no statistical analysis was carried out in the BLM and RTM+BLM groups due to the small numbers of patients. At the same time, there was a progressive decrease in the levels of anti-double-stranded DNA (ds-DNA) antibodies (Abs) and an increase in the concentration of the complement fractions C3 and C4 in the RTM and RTM+BLM groups (p < 0.05) at one-year follow-up. After 12 months of therapy with BAs, there was a decrease in IgG (p < 0.02) and IgM (p < 0.03) levels; but overall it remained within the reference ranges. Prior to therapy, irreversible organ damages were recorded in 23 (42.6%) of the 54 patients. The increased damage index at 12 month was observed only in patients receiving RTM, which is probably due to the use of higher-dose glucocorticoids.Conclusion. All three methods of therapy with BAs in SLE patients demonstrated good efficiency shown as a significant decrease in clinical and laboratory activity measures that were assessed by SLEDAI-2K and the levels of anti-ds-DNA and complement components C3 and C4. The decrease in immunoglobulin levels did not go beyond the reference values. Therapy with BLM and RTM+BLM allowed for managing patients with the low and average doses of oral glucocorticoids, which contributed to the reduction of not only the activity, but also risk of irreversible organ damages.

The NET-effect of combining rituximab with belimumab in severe systemic lupus erythematosus

ObjectiveIn systemic lupus erythematosus (SLE) patients, excessive formation of neutrophil extracellular traps (NETs) is observed and their degradation is impaired. In vitro, immune complexes (ICx) trigger NET formation while NET-derived DNA is a postulated autoantigen for anti-nuclear autoantibodies (ANAs), found in SLE. Based on these self-perpetuating mechanisms in SLE, this study investigates whether interfering with ICx formation using a combination of rituximab (RTX) and belimumab (BLM) could decrease NET formation and ameliorate disease. MethodsA phase 2A, open-label, single arm proof-of-concept study was performed wherein 16 SLE patients with severe, refractory disease were treated with a combination of CD20-mediated B-cell depletion with rituximab and sustained inhibition of B-cell activating factor BlyS with belimumab. Besides safety, the study's endpoints were chosen to address the concept of autoantibodies in relation to excessive NET formation. ResultsWe demonstrated a surge of BlyS levels upon RTX-mediated B-cell depletion which was abrogated by subsequent BLM treatment. As such, therapeutic intervention with RTX + BLM led to specific reductions in ANAs and regression of excessive NET formation. RTX + BLM appeared to be safe and achieved clinically significant responses: low lupus disease activity state was achieved in 10 patients, renal responses in 11 patients and concomitant immunosuppressive medication was tapered in 14 out of the 16 patients. ConclusionsThis study provides novel insights into clinical beneficence of reducing excessive NET formation in SLE by therapeutic targeting ANA production with RTX + BLM. Altogether putting forward a new treatment concept that specifically ameliorates underlying SLE pathophysiology. Trial registrationClinicalTrials.gov NCT02284984.

EXPERIENCE WITH EFFECTIVE COMBINED ANTI-B-CELL THERAPY WITH RITUXIMAB AND BELIMUMAB FOR REFRACTORY GRANULOMATOSIS WITH POLYANGIITIS (WEGENER'S) WITH SEVERE LUNG DAMAGE

Systemic vasculitis (SV) associated with antineutrophil cytoplasmic antibodies (ANCA) is characterized by severe multiple organ lesions with a poor prognosis. The successful introduction of standard therapy with cyclophosphamide (CP) and innovative anti-B-cell therapy with rituximab (RTM) for the treatment of ANCA SV gives no grounds to stop further searching for effective and safe therapy since about 10–15% of patients with ANCA SV are refractory to standard therapy with CP; after the latter, approximately 40% of patients develop recurrences, and granulomatous inflammation in the respiratory organs in granulomatosis with polyangiitis (GPA) can be resistant to RTM treatment, especially following its single cycle. There is increasing evidence that the efficiency of anti-B-cell therapy can be enhanced by adding belimumab (BLM). The paper describes a clinical case of effective sequential combined anti-B-cell therapy with BLM and RTM for remission induction in a female patient who has GPA with severe granulomatous lung injury refractory to previous therapy with CP (a total dose of 6.2 g) and a single cycle of therapy with RTM (a total dose of 2.6 g). BLM was used 12 months after RTM administration because there were no positive changes in lung injury. At 12 months after initiations of treatment with BLM (800 mg twice at a weekly interval, then 800 mg monthly), there was a substantial reduction in the lung parenchymal foci, as evidenced by multislice spiral computed tomography (MSCT); and the treatment was continued for another 6 months, thereafter discontinued due to the occurrence of ulcerative stomatitis. After its relief, RTM was again given at reduced dose cycles of 500 mg every 6 months; lung MSCT showed further improvement and remission achieved. BLM may be effective in treating the GPA patients who are refractory to CP and have an insufficient response to RMT treatment. Combined anti-B-cell therapy aimed at depleting SD20+ B-cells and at blocking BAFF may be a promising area for the treatment of patients with ANCA SV.

THE TIME COURSE OF CHANGES IN B LYMPHOCYTE SUBPOPULATIONS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS DURING THERAPY WITH BIOLOGICAL AGENTS

Objective: to study the baseline level and time course of changes in peripheral blood B cell subpopulations in patients with systemic lupus erythematosus (SLE) versus the clinical manifestations of the disease during therapy with rituximab (RTM) and belimumab (BLM). Subjects and methods. 49 patients with a documented diagnosis of SLE and high and moderate SLEDAI-2K values were divided into three groups: 1) 40 patients received RTM, 2) 5 patients took BLM; 3) 4 patients had combination therapy (dual anti-B-cell therapy) with RTM + BLM. Peripheral blood B lymphocyte subpopulations were measured by multicolor flow cytometry using a panel of monoclonal antibodies against surface membrane markers of B lymphocytes; the patients underwent clinical immunological examination before therapy with biological agents and every 3 months during a year. Results and discussion. Patients with high SLE activity (SLEDAI-2K 18±5) and involvement of vital organs had generally higher levels of double negative memory cells (r = 0.52; p < 0.001) with relatively low counts of naive B cells (r=-0.54; p < 0.0007) than those without severe organ pathology (SLEDAI-2K 8±2). RTM therapy at 3 month of follow-up resulted in a noticeable decrease in the number of naive and double negative memory B cells and to a lesser extent in that of non-switched and switched memory B cell. A rapid recovery of the count of memory B cells and plasmablasts after a RTM cycle at 6 months after therapy initiation should be evaluated as a predictor of early exacerbation of SLE. There was a reduction in the clinical and laboratory signs of SLE activity, as well as inhibition of naive B cells, plasma cells, and plasmablasts in all the 5 patients receiving BLM at various stages of follow-up. Dual anti-B cell therapy most effectively reduced disease activity at 3 months, prolonged the achieved remission, contributed to the achievement and maintenance of a low B lymphocyte level at later stages of control, to the further decline in the number of plasmablasts and plasma cells, and prevented the synthesis of autoantibodies. Conclusion. Assessment of the time course of changes in peripheral blood B lymphocyte subpopulations provides new opportunities to identify impaired function and regulation of cellular immunity in patients with SLE, it may be a useful diagnostic parameter to monitor an autoimmune disease and a valuable tool to assess and predict a response.

Belimumab withdrawal

Belimumab withdrawal

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.

EXPERIENCE WITH BELIMUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Objective: to investigate the efficacy of an anti-BlyS drug (belimumab) for the treatment of systemic lupus erythematous (SLE). Subjects and methods. Belimumab (BLM) was administered to three patients with SLE (two women and one man were aged 24, 28, and 39 years, respectively). SLE activity was estimated according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, the values of which were 8, 12, and 14 scores, respectively, due to high immunological activity, skin, joint, and mucosal lesions. The high Systemic Lupus International Collaborating Clinics (SLICC) Damage Index score of 3 was found in 2 of the 3 patients. All patients received glucocorticoids (GC) 20–25 mg/day; two – hydroxychloroquine and one – mycophenolate mofetil 1000 mg/day. Therapy with BLM was performed using a standard scheme: three 10 mg/kg infusions during the first month, then one infusion every month. Results. Positive clinical changes were noted 2 months after therapy initiation; symptoms completely disappeared 3 and 6 months later. Anti-DNA antibodies and complement fractions, the levels of which were partially normalized at 2 to 9 months of treatment, were most refractory to BLM therapy. During the follow-up, there were no SLE exacerbations; the dose of GC could be halved in two cases. Glomerular filtration normalized in one patient with inactive lupus nephritis. Conclusion. BLM treatment is justified in patients with moderate SLE activity in the presence of polyarthritis, serositis, skin and mucosal lesions and with high immunological activity. The use of BLM is not contraindicated in patients with inactive lupus nephritis without obvious kidney dysfunction. The additional motivation to use BLM may be an inadequately high GC dose, a recurrent disease course, insufficient therapeutic efficiency, and a risk for irreversible organ damages

Belimumab: targeted therapy for systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease,whose exact pathogenesis is not fully clear as yet.The abnormal activation of B cells plays an important role in the development of SLE,and B cell-activating factor (BAFF) is critical for the abnormal activation of B cells.Belimumab is a human monoclonal antibody which can selectively recognize and block soluble BAFF.The efficacy and safety of belimumab have been confirmed for the treatment of SLE in randomized,double-blind,large-scale clinical trials.As a biological agent with high efficacy,few side effects and high tolerability,belimumab is a promising drug for SLE. Key words: Lupus erythematosus, systemic; Belimumab; Molecular targeted therapy

FRI0375 A Delphi Exercise for Treatment Algorithms for Systemic Lupus Erythematosus

BackgroundTreatment for SLE is often organ based. The literature lacks trials and consensus for treatment in SLE when standard first or second line care is ineffective.ObjectivesTo determine expert consensus for...

AB0368 Systematic review of efficacy and safety of biological therapies in lupus nephritis

ObjectivesThe aim of this study is to analyze the efficacy and safety of 10 biological therapies (BT) for lupus nephritis. These therapies are infliximab (IFX), etanercerpt (ETN), adalimumab (ADA), golimumab...

Development of targeted therapeutic agents for systemic lupus erythematosus

With the development of immunology and molecular-biology,great advances have been made in biological therapies targeted at the immunopathological mechanisms or directed against some targets in systemic lupus erythematosus (SLE) in the past decade.These biological agents,with belimumab as a representative,have offered a new approach to the treatment of SLE.At present,there are nearly 20 targeteddrugs for SLE that undergo preclinical research or clinical trials.According to the difference in action targets,they are mainly divided into seven categories:B-cell-targeted drugs,T-cell/costimulatory molecule-targeteddrugs,cytokine inhibitors,innate immunity-targeted drugs,tolerogens,inhibitors of cell surface receptors,and other targeted agents including monocyte chemoattractant protein 1/monocyte chemoattractant CC chemokineligand 2 inhibitors,N-acetyl cysteine,etc. Key words: Lupus erythematosus, systemic; Antibodies, monoclonal; Therapy