Frequency and predictors for early-achieved lupus low disease activity state in systemic lupus erythematosus patients treated with telitacicept or belimumab: A real-life, single-center observational study.

Objective: To collect real-world data regarding the attainment of the early-achieved lupus low disease activity state (LLDAS) in systemic lupus erythematosus (SLE) patients receiving telitacicept or belimumab treatment, and identify factors predictive of target achievement. Methods: Eighty-seven SLE patients who received telitacicept (N=42) or belimumab (N=45) were retrospectively reviewed in this observational study. Clinical and laboratory data, disease activity assessment, and glucocorticoid dosage were collected for analysis. Achieving LLDAS at least once within 24 weeks post-treatment was considered as early-achieved LLDAS. Multivariate regression was used to assess baseline predictive variables for early-achieved LLDAS. Subgroup analysis and interaction tests were also performed to examine the robustness of the results across different sets of baseline characteristics. Prognostic stratification for early-achieved LLDAS was established based on the identified risk factors. Results: During the 24-week follow-up period, LLDAS was achieved by at least one time in 49.43% (43/87) of the patients, with sustained achievement through week 24 observed in 36 out of these 43 patients (83.27%). Multivariate analysis revealed that early achievement of LLDAS was particularly observed in patients with higher baseline lymphocyte counts [HR=1.79, 95% CI (1.19-2.67), P=0.005]and serum albumin levels [HR=1.06, 95% CI (1.003-1.12), P=0.039]. Conversely, hematological involvement [HR=0.48, 95% CI (0.24-0.93), P=0.031] predicted lower attainment of early-achieved LLDAS. The use of telitacicept was associated with a reduced risk of failing to attain early achievement of LLDAS [HR=2.55, 95% CI (1.36-4.79), P=0.004]. Subgroup analyses and interaction tests showed a stable relationship between the telitacicept use and LLDAS achievement. The results remained consistent across all subgroup analyses. Significant differences (P<0.001) were observed in the Kaplan-Meier estimates for LLDAS among risk groups based on the number of identified risk factors. Conclusion: The achievement of LLDAS is attainable in the management of SLE patients undergoing treatment with telitacicept or belimumab in real-life clinical practice. Baseline lymphocyte counts, serum albumin levels, hematological involvement and the use of telitacicept serve as robust predictors for early-achieved LLDAS, helping to identify patients who are likely to benefit on the treatment.

Monoclonal antibodies targeting interleukins for systemic lupus erythematosus: updates in early clinical drug development.

INTRODUCTION: The advent of biological therapies has already revolutionized treatment strategies and disease course of several rheumatologic conditions, and monoclonal antibodies (mAbs) targeting cytokines and interleukins represent a considerable portion of this family of drugs. In systemic lupus erythematosus (SLE) dysregulation of different cytokine and interleukin-related pathways have been linked to disease development and perpetration, offering palatable therapeutic targets addressable via such mAbs. AREAS COVERED: In this review, we provide an overview of the different biological therapies under development targeting cytokines and interleukins, with a focus on mAbs, while providing the rationale behind their choice as therapeutic targets and analyzing the scientific evidence linking them to SLE pathogenesis. EXPERT OPINION: An unprecedented number of clinical trials on biological drugs targeting different immunological pathways are ongoing in SLE. Their success might allow us to tackle present challenges of SLE management, including the overuse of glucocorticoids in daily clinical practice, as well as SLE heterogenicity in treatment response among different individuals, hopefully paving the way toward precision medicine.

Belimumab concentration measurements using a homologous anti-idiotype immunoassay.

Monitoring belimumab concentrations in patients can be a valuable tool for assessing treatment response and for personalizing drug doses. Various assay formats may be used to measure concentrations of therapeutic monoclonal antibodies. A particularly useful format involves the use of anti-idiotype monoclonal antibodies, selected to be highly specific to the antibody of interest. Here, we describe the development of a specific, high-affinity anti-idiotype antibody to belimumab, and the application of this antibody in a homologous sandwich ELISA to measure belimumab concentrations.

A Comprehensive and Practical Approach to the Management of Lupus Nephritis in the Current Era.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is one of the leading causes of morbidity and mortality in patients with SLE. It is estimated that up to 60% of individuals with SLE will develop LN, which can manifest at any stage of a patient's life; however, it commonly emerges early in the course of SLE and tends to exhibit a more aggressive phenotype in men compared to women. Black and Hispanic patients are more likely to progress to kidney failure than white patients. LN is characterized by kidney inflammation and chronic parenchymal damage, leading to impaired kidney function and potential progression to kidney failure. This article provides a comprehensive overview of the epidemiology, pathogenesis, clinical presentation, diagnosis, and management of LN, highlighting the importance of early recognition and treatment of LN to prevent progressive, irreversible kidney damage and improve patient outcomes. Additionally, the article discusses current and emerging therapies for LN, including traditional immunosuppressive agents, biological agents, and novel therapies targeting specific pathways involved in LN pathogenesis, to provide a practical guide for clinicians in properly diagnosing LN and determining a patient-centered treatment plan.

Improved Health Outcomes in Patients with Systemic Lupus Erythematosus Following Early Belimumab Initiation Without Prior Immunosuppressant Use: A Real-World Descriptive Study.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have variable treatment pathways, including antimalarials, glucocorticoids, immunosuppressants, and/or biologics. This study describes differences in clinical outcomes when initiating belimumab (BEL) before and after immunosuppressant use. METHODS: This real-world, retrospective cohort study (GSK Study 217536) used de-identified administrative claims data from January 2015 to December 2022 in the Komodo Health Database. Adults with moderate/severe SLE initiating BEL (index date) were identified from January 2017 to May 2022, allowing a ≥ 24-month baseline period. Patients were stratified into those initiating BEL before immunosuppressant use (no immunosuppressant use within 24 months before index) and those initiating BEL after immunosuppressant use (one immunosuppressant used within 24 months before index). Oral glucocorticoid (OGC) use, SLE flares, new organ damage, and all-cause healthcare resource utilization (HCRU) were analyzed descriptively over a 24-month follow-up. RESULTS: Baseline SLE severity was similar for patients initiating BEL before (n = 2295) versus after (n = 4114) immunosuppressant use (moderate, 83.1% vs 79.0%; severe, 16.8% vs 21.0%). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates and OGC use. Post-index, patients initiating BEL before versus after immunosuppressant use discontinued their OGC sooner (moderate baseline SLE, 4.5 vs 8.9 months; severe baseline SLE, 6.2 vs 11.6 months). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates per person-year at all time points (especially severe flare rates in patients with severe baseline SLE, 0.70 vs 1.48 through 24 months post-index). Median time to new organ damage occurrence was longer in patients initiating BEL before versus after immunosuppressant use (moderate baseline SLE, 32.1 vs 26.7 months; severe baseline SLE, 22.7 vs 21.6 months). All-cause HCRU was similar between cohorts. CONCLUSIONS: These results suggest that patients initiating BEL before versus after immunosuppressant use had more favorable outcomes.

Early effectiveness and safety analysis of belimumab in addition to standard treatment in patients with systemic lupus erythematosus.

Objectives: This study aimed to evaluate the early effectiveness and safety of belimumab in addition to standard therapy in patients with systemic lupus erythematosus (SLE) for 24 weeks. Patients and methods: This retrospective study was conducted with 60 adult patients with active SLE between June 2020 and August 2022. The patients either received intravenous belimumab in addition to standard therapy (n=31; 24 females, 7 males; mean age: 33.7±14.1 years; range, 18 to 52 years) or only standard therapy (n=29; 22 females, 7 males; mean age: 34.1±13.4 years; range, 19 to 66 years) for 24 weeks. Outcome measures, including safety and effectiveness (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index [SELENA-SLEDAI]), changes in biomarkers (double-stranded DNA [deoxyribonucleic acid]), serum complement levels, and immunoglobin G (IgG) were recorded. Adverse events were recorded. Results: Baseline demographic and clinical characteristics were similar between the two groups. More patients in the belimumab group achieved a reduction of ≥4 points in SELENA-SLEDAI at weeks 12 and 24 (week 12, 77.4% vs. 41.4%, p=0.008; week 24, 87.1% vs. 48.3%, p=0.002). The mean score of SELENA-SLEDAI was significantly lower in the belimumab group compared to the standard therapy group at week 12. However, a significant difference was not reached at week 24. Moreover, mean levels of serum C3 and C4 in the belimumab group were significantly higher than those in the standard therapy group at weeks 12 and 24. A higher proportion of patients in the belimumab group had a normal C3 level than in the standard therapy group. In addition, belimumab treatment resulted in a significant decrease in IgG levels at both weeks 12 and 24. At week 24, the belimumab group had a higher reduction in prednisone dose than the standard therapy group. Furthermore, the percentages of patients with more than 50% reduction in prednisone over baseline were significantly greater for belimumab versus standard therapy at week 12 (p=0.002). The occurrence of adverse events was similar between the two groups (standard therapy group, 44.8%; belimumab group, 51.6%). Conclusion: Intravenous belimumab was well tolerated and significantly improved disease activity in Chinese patients with SLE at the early stage of treatment. More importantly, belimumab treatment could result in a rapid reduction in prednisone dose as early as week 12.

Effects of belimumab on the lipid profile in systemic lupus erythematosus patients: an observational study.

This study is asked to investigate the effects of belimumab on the lipid profile in systemic lupus erythematosus (SLE) patients. Forty-one SLE patients who received at least 6 months of belimumab treatment were retrospectively analyzed. The control group consisted of 56 age- and sex-matched lupus patients not treated with belimumab. The changes in lipid profile after a 6-month treatment were compared between the two groups. Generalized estimating equation (GEE) analyses were performed to examine lipid levels longitudinally during the period and the effect of clinical response variables and medication on the lipid profile in the belimumab group. In the belimumab group, high-density lipoprotein (HDL) cholesterol levels increased significantly after the 6-month treatment (P = 0.02). After 1 month, HDL, apolipoprotein A-I (apoA-I) significantly increased by 13.8 and 11.4%, compared with baseline, respectively. After 3 months, HDL and apoA-I increased by 9.0 and 7.1%, respectively. After 6 months, HDL increased by 7.6% compared with baseline. Total cholesterol, triglycerides, low-density lipoprotein cholesterol, and apolipoprotein B did not change significantly over the course of treatment. GEE analyses indicated a significant association between HDL and disease activity indexes, such as IgG, anti-dsDNA, and complement C3. Subgroup analysis revealed significant changes in HDL only in patients who had achieved a ≥ 4-point reduction in SLEDAI-2 K after 6 months of belimumab treatment. Belimumab treatment may result in a long-term increase in HDL level in SLE patients by improving control of lupus activity. This might have beneficial effects on controlling cardiovascular risk in lupus patients. Key Points • Treatment with belimumab resulted in a significant and sustained increase in the HDL levels in SLE patients. • Significant changes in HDL were observed in lupus patients treated with belimumab who had a better clinical response.

Efficacy and safety of belimumab combined with the standard regimen in treating children with lupus nephritis.

The purpose of this study is to evaluate the efficacy and safety of belimumab combined with the standard regimen in treating children with active lupus nephritis. This single-center, retrospective cohort study used clinical data of children with newly active lupus nephritis hospitalized in the Department of Nephrology between December 2004 and February 2023. Patients were divided into a belimumab or traditional treatment group according to whether or not they received belimumab. Renal remission and recurrence rates and glucocorticoid dose were compared between groups. Forty-seven children (median age 11 years) were enrolled, including 30 and 17 children in the traditional treatment and belimumab groups, respectively. The Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) score of children in the belimumab group (23.59 ± 7.78) was higher than that in the traditional treatment group (19.13 ± 6.10) (P = 0.035). The two groups showed no significant difference in the frequency of pyuria, gross hematuria, and the levels of 24-h proteinuria and estimated glomerular filtration rate. The complement C3/C4 in the belimumab group recovered faster than that in the traditional treatment group (P < 0.05). There were no between-group differences in the complete renal remission rate at 6 or 12 months (P = 0.442, P = 0.759). There were no between-group differences in 1-year recurrence rate (P = 0.303). Furthermore, 6 and 12 months after treatment, glucocorticoid doses were lower in the belimumab than the traditional treatment group (17.87 ± 6.96 mg/d vs. 27.33 ± 8.40 mg/d, P = 0.000; 10.00 (5.3) mg/d vs. 13.75 (10.0) mg/d, P = 0.007), respectively. CONCLUSION: With an equivalent renal remission rate, belimumab combined with the standard traditional regimen might promote the tapering of glucocorticoids, and the incidence of adverse events is low. WHAT IS KNOWN: • Belimumab is documented as an adjunctive treatment with systemic lupus erythematosus (c-SLE) LN with efficacy. • Due to the paucity of studies, its effects and side effects in children with LN remain unclear. WHAT IS NEW: • This single-center, retrospective cohort study evaluated the efficacy and safety of belimumab combined with the standard regimen in treating children with proliferative LN. • Belimumab combined with the standard traditional treatment might promote the tapering of glucocorticoids, while exhibiting a low occurrence of adverse events.

Belimumab-induced periungual pyogenic granulomas: A case report.

Pyogenic granuloma (PG) is a benign vascular neoformation, presenting as a painful red nodule on the skin, mucosa or nail apparatus. It is usually related to local complications such as bleedings and superinfections. The etiology of PG remains still unclear, and several triggers can lead to its formation. In case of multiple lesions, systemic conditions and drugs remain the main causes. Antineoplastic treatments, retinoids, antiretrovirals, hormones and anticonvulsants are frequently implicated in PG formation. In literature, PG has been rarely described in the course of biological treatment due to rheumatological disease. The present case report describes the development of polydactolous PGs in a 21-year-old woman with juvenile systemic lupus erythematosus (jSLE) during treatment with belimumab, a monoclonal antibody directed against BlyS. The clinical presentation, in particular the timing and the multiplicity of the lesions, and the improvement after belimumab discontinuation allowed us to consider PG as drug-induced. This case highlights the importance of considering PG as a potential complication of rheumatologic treatments.

Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

Do we really need cyclophosphamide for lupus nephritis?

A 14-year-old patient presents with hematuria and proteinuria. Clinical evaluation reveals a positive anti-nuclear antibody titer, positive anti-double stranded DNA antibody and hypocomplementemia. Systemic lupus erythematosus (SLE) is diagnosed based on the 2019 EULAR/ACR (European League Against Rheumatism/American College of Rheumatology) classification criteria (Aringer et al. Arthritis Rheumatol 71:1400-1412, 2019). A kidney biopsy is performed that confirms the presence of immune complex glomerulonephritis, ISN-RPS (International Society of Nephrology/Renal Pathology Society) class IV (Bajema et al. Kidney Int 93:789-796, 2018). According to the latest clinical practice guidelines (Rovin et al. Kidney Int 100:753-779, 2021; Fanouriakis et al. Ann Rheum Dis 83:15-29, 2023), there are alternatives to treating this patient with cyclophosphamide. But what if this patient also presented with oliguria and volume overload requiring intensive care and dialysis? What if this patient also presented with altered mental status and seizures, and was diagnosed with neuropsychiatric lupus? What if this patient was also diagnosed with a pulmonary hemorrhage and respiratory failure? The clinical practice guidelines do not address these scenarios that are not uncommon in patients with SLE. Moreover, in some countries worldwide, patients do not have the privilege of access to biologics or more expensive alternatives. The purpose of this review is to evaluate the contemporary options for initial treatment of nephritis in patients with SLE.

Considering belimumab during pregnancy: A more viable option over time.

OBJECTIVE: To share our experience with belimumab in lupus pregnant women and to review the relevant published literature on its use in this scenario. METHODS: A prospective observational study of pregnant patients with lupus was conducted. Additionally, MEDLINE and EMBASE databases were searched, and a secondary hand search of the literature was performed. Studies were evaluated and visualised descriptively. RESULTS: Sixteen pregnancies of 12 lupus women were included, six (involving eight pregnancies) received belimumab throughout their illness, five of them during some period of gestation. In this group, there was one miscarriage, one elective termination and seven live foetuses (including two live twins). There was one type I intrauterine growth retardation, and a preterm pregnancy due to premature rupture of membranes (PPROM). One mild lupus flare was detected. There were no cases of pre-eclampsia, gestational diabetes mellitus or hypertension. All neonates had normal Apgar scores at birth, none needed critical care. There were no congenital anomalies. After the search, we identified 10 case reports and case series, and five registries. Among the 39 reported cases (41 pregnancies), there were 5 PPROM, 4 pre-eclampsia, and 1 eclampsia. All women made full recoveries. Nineteen new-borns had low birth weight. There were no malformations. While registries did not indicate an increased risk of birth defects or pregnancy loss, there was a higher risk of neonatal infections. CONCLUSIONS: Belimumab may be an option for pregnant women with difficult-to-control lupus. Further research is needed to confirm the absence of association between belimumab and foetal harm.

Belimumab corticosteroid-sparing treatment in systemic lupus erythematosus: a real-life observational study (BESST study).

Data about the impact of Belimumab on corticosteroid sparing in real life are scarce. To assess the corticosteroid-sparing effect among patients with systemic lupus erythematosus (SLE) treated with Belimumab in real-life settings. Multicentric observational retrospective study including patients with SLE and having received Belimumab for at least 6 months between 2011 and 2020, in eight French hospitals. "Low dose" referred to patients receiving up to 7.5 mg of prednisone a day and "Very low dose" to those receiving strictly ≤ 5 mg prednisone a day The primary endpoint was the reduction of daily prednisone dose after six months of Belimumab. The secondary endpoint was a change in the proportion of patients with low or very low dose of prednisone as well as those without prednisone during the Belimumab course. Censoring occurred for patients who stopped Belimumab. Bivariate analyses were performed using the Wilcoxon signed-rank test. The threshold for statistical significance was set at p < 0.05. Thirty patients were included. All were female with a median age of 38 years. A significant reduction in prednisone dose was observed at month 6 (10 [7-20] vs 6.75 [2-9] mg, p < 0.0001), continued until month 12 (10 [7-20] mg vs 5 [0-7.12] mg, p < 0.001) and was sustained until month 24. The proportion of patients with very low dose of prednisone and those without prednisone progressively increased during the Belimumab course. Introducing Belimumab in patients with SLE, in real-life conditions, is associated with early and sustained corticosteroid-sparing effect.

No clear influence of treatment escalation on flare prevention in serologically active clinically quiescent patients with systemic lupus erythematosus: a retrospective cohort study.

This study aimed to clarify the efficacy and safety of treatment escalation by initiating therapeutic agents in serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE). We retrospectively evaluated SACQ patients with SLE for ≥ 180 days, with the introduction of a therapeutic agent for SLE defined as exposure. The efficacy endpoints included the time to flare and time to remission, whereas the safety endpoint was the incidence of adverse events. The efficacy endpoints were assessed via Cox proportional hazards model with time-dependent covariates, which included exposure, serological activity, and prednisolone dose. Among 109 SACQ patients, 24 were initiated on the following therapeutic agents for SLE: hydroxychloroquine (10 patients), belimumab (6 patients), and immunosuppressive agents (8 patients). A total of 37 patients experienced a flare (8 and 29 patients during exposure and nonexposure periods, respectively). The time to flare was comparable between the exposure and control groups. Among 68 patients who were not in remission at the start of observation, 27 patients achieved remission (5 and 22 patients during exposure and nonexposure periods, respectively). Although both groups had a similar time to remission, the exposure group treated with belimumab had a significantly higher rate of remission than the control group. The adverse events were more frequent during the exposure period than during the nonexposure period. Thus, this study did not reveal a clear influence of treatment escalation on flare prevention and remission achievement.

Successful treatment of lupus protein-losing enteropathy with belimumab: A case report.

Lupus protein-losing enteropathy (LUPLE) is a rare condition in patients with systemic lupus erythematosus (SLE). Since the causes and exact pathological mechanism have not been elucidated, appropriate treatment has not been determined. Here, we report the case of a 69-year-old woman with systemic lupus erythematosus who developed LUPLE which was successfully treated with belimumab without an increase in glucocorticoid dose. This case suggests that belimumab monotherapy may be a treatment option for LUPLE.

Thorough assessment of the effectiveness of belimumab in a large Spanish multicenter cohort of systemic lupus erythematosus patients.

OBJECTIVES: To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles. METHODS: A longitudinal retrospective multicentre cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed. RESULTS: A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. Twenty-seven-point two percent of patients were in DORIS ≥ 50% of the visits and a 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC. CONCLUSION: Our study not only demonstrates belimumab´s efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual.

Glucocorticoid-free remission in patients with SLE in the era of biologics: Immune complex disease is likely to benefit from current medications.

OBJECTIVES: In addition to various immunosuppressive agents, belimumab and anifrolumab became available in Japan. We aimed to investigate glucocorticoid-free clinical remission in a single-centre retrospective cohort in October 2023. METHODS: Our cohort included patients with SLE who needed to start or increase glucocorticoids for disease activity and were followed up for more than 1 year. We investigated the rate of achievement of clinical remission off corticosteroids (CR off C), defined as no clinical score on the SLEDAI-2K without glucocorticoids, baseline predictors of CR off C, medications used when CR off C was achieved, and flare rates following CR off C. RESULTS: Out of the 60 patients followed for an average of 5.4 (±2.6) years, 17 (28.3%) achieved CR off C in 3.6 (±1.2) years after enrolment. Use of belimumab and anifrolumab accounted for eight (47.1%) of the achievers. Among the baseline data, male sex, recent enrolment, high glucocorticoid dose, and detection of immune complex (IC) significantly predicted CR off C, while lupus nephritis (LN) and a low C3 level tended to predict it. In the multivariate analysis, IC detection was the only predictor of CR off C. Clinical flares were observed in 5.9% of the achievers during a median 1.2 years after achievement of CR off C. CONCLUSION: In the era of biologics, CR off C was achieved in 28.3% of the patient cohort requiring the start or increase of glucocorticoids for disease activity, with a relatively low rate of flares, suggesting that glucocorticoid-free clinical remission is an achievable target in SLE. IC disease, represented by male sex or nephritis, is likely to benefit from currently available medications.

Usefulness of Belimumab in Adult Patients With Systemic Lupus Erythematosus Evaluated Using Single Indexes: A Meta-Analysis and Systematic Review.

Background: Belimumab is the first antibody drug approved for systemic lupus erythematosus (SLE), and is a fully human monoclonal antibody that inhibits soluble B lymphocyte stimulator protein. In clinical trials, a composite index was used to assess efficacy of belimumab. However, clinical guidelines on SLE treatment currently use single efficacy indexes. Objective: The main objective of this study was to perform a meta-analysis to evaluate the efficacy of belimumab utilizing single indexes used in routine clinical practice, rather than the composite efficacy index used in clinical trials during the development phase. As a secondary endpoint, safety was also evaluated. Methods: Several databases were searched to identify reports published up to December 1, 2021 on randomized controlled trials examining the efficacy of belimumab in adult patients with SLE. From the clinical trial data, efficacy was evaluated using single indexes including the SLE Disease Activity Index (SLEDAI), British Isles Lupus Assessment Group Index, and Physician Global Assessment. Safety was also assessed. Data were synthesized and analyzed using Review Manager 5.4. This study protocol was registered in the UMIN Clinical Trials Registry (Registration number: UMIN000052846). Results: The search identified 12 reports that met the inclusion criteria. Five reports were included in efficacy evaluation and 9 in safety evaluation. The primary endpoint was SLEDAI. Significantly more belimumab-treated patients achieved a ≥4-point reduction in SLEDAI (relative risk 1.28; 95% confidence interval, 1.16-1.40; P < 0.00001) compared with placebo. Other efficacy endpoints were also improved significantly in the belimumab group. No difference in safety was found between belimumab and placebo. Conclusions: The present meta-analysis evaluating clinical trial data using various single indexes recommended by clinical guidelines for SLE verifies that addition of belimumab to standard of care is efficacious for moderate-to-severe SLE.