Studies supporting therapeutic drug monitoring to biopharmaceuticals in SLE are scarce. We aimed to assess anti-drug antibody (ADA) occurrence in belimumab-treated SLE patients and associations between belimumab concentrations and clinical response, serological outcomes and adverse events.

We included 100 patients treated with intravenous belimumab. Clinical data and biological samples were collected at baseline and months 3, 6, 12 and 24. Belimumab levels were determined by quantitative sandwich ELISA, and ADA by an acid-dissociation radioimmunoassay. Clinical activity was evaluated with the SLEDAI-2000 (SLEDAI-2K), revised SLE activity measure (SLAM-R) and physician's global assessment (PhGA). Serological markers included C3, C4 and anti-dsDNA. We performed cross-sectional Spearman's rank correlation analyses, and longitudinal analyses using generalized estimating equations.

Belimumab concentrations varied widely (median: 25.8; interquartile range [IQR]: 20.9-43.5 μg/ml) but were stable over time at the group level. Pre-existing ADA was detected in two patients, but no patient developed ADA during follow-up. Belimumab levels moderately correlated with SLEDAI-2K (ρ: -0.37; P = 0.003) and PhGA (ρ: -0.41; P = 0.005) at month 6, while longitudinal analysis revealed a very weak association with SLEDAI-2K (β: -0.10; SE: 0.05; P = 0.031) and a weak association with SLAM-R (β: -0.32; SE: 0.13; P = 0.014). Despite moderate correlations between belimumab levels and serological markers at month 6, there were no associations in longitudinal analysis. There was no relationship between belimumab levels and adverse events.

Belimumab yielded no immunogenicity. Belimumab levels were modestly associated with clinical activity but not with serological activity or adverse events.

DORIS remission, based on clinical activity, and lupus low disease activity state (LLDAS), which includes serological markers, are protective targets in SLE. However, it remains unclear whether their prognostic impact is influenced by serum anti-dsDNA and complement levels.

We analysed data from five phase III trials (BLISS-52, BLISS-76, BLISS-SC, BLISS-NEA, EMBRACE) totalling 45 254 monthly visits. Generalized linear models evaluated the effects of DORIS/LLDAS-with or without active serology-on the risk for severe (BILAG ≥1A/2B) and renal (BILAG A/B) flares. Organ damage was also assessed.

Normal serology occurred in 544/1871 (29.1%) DORIS and 1879/4760 (39.5%) LLDAS visits. Using no-DORIS as reference, DORIS with anti-dsDNA(-) or normal/high C3/C4 demonstrated stronger protection against severe flares (odds ratio [OR] 0.042 [95% CI: 0.005, 0.331] and 0.216 [95% CI: 0.094, 0.494], respectively) compared with DORIS with anti-dsDNA(+) or low C3/C4 (OR 0.511 [95% CI: 0.284, 0.919] and 0.528 [95% CI: 0.261, 1.067]). Similarly, LLDAS with normal serology showed greater risk-reduction in severe flares compared with LLDAS with active serology, especially low C3/C4. For renal flares, DORIS with serological activity carried ∼6-fold higher risk compared with combined clinical/serological remission (OR 5.94 [95% CI: 1.26, 28.04]). Damage accrual was lowest in patients with sustained DORIS and ≥1 visit showing anti-dsDNA(-) (0.8%) or normal C3/C4 (1.8%).

Normal serology enhances the protection of DORIS and LLDAS against severe and renal SLE flares, possible reflecting deeper states of disease control. Patients with recently active disease who meet clinical targets but have persistently abnormal serology may require close monitoring to minimize flare-risk.

We aimed to evaluate the risk of infectious complications of Belimumab with standard care in systemic lupus erythematosus (SLE).

We searched PubMed, Web of Science, EMBASE, and Cochrane databases for studies on SLE and Belimumab and evaluated the study quality using the Cochrane Collaboration tool (ROB 2). A random-effect model was employed to analyze the results. To evaluate publication bias, Egger's tests were used. We also performed subgroup analysis based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and British Isles Lupus Assessment Group(BILAG). The study protocol has been registered in PROSPERO (CRD42023421255).

Eight studies involving 8545 patients were included, of which four studies had a high attrition bias. The present study suggested that the risks of infectious complications including infection (RR=1.02, 95 %CI=(0.97,1.08), I2=7.7 %) or serious infections (RR=0.94, 95 %CI=(0.77,1.15), I2=0 %), nasopharyngitis(RR=1.02, 95 %CI=(0.79,1.33), I2=36 %), upper respiratory tract infection(RR=0.97, 95 %CI=(0.83,1.14), I2=20.6 %), urinary tract infection(RR=1.09, 95 %CI=(0.91,1.32), I2=0 %), herpes zoster (RR=0.75, 95 %CI=(0.54,1.05), I2=0 %)and influenza(RR=0.98, 95 %CI=(0.69,1.39), I2=0 %) were not significantly increased in patients who received Belimumab with standard care, except for bronchitis (RR=1.51, 95 %CI=(0.98,2.33), I2=23.7 %). Additionally, the subgroup analysis of SLEDAI and the proportion of patients with BILAG 1A/2B did not show any significant impact on infectious complications.

Meta-analysis results demonstrated that intravenous (IV) Belimumab(≤10 mg/kg), along with standard care, did not significantly increase the risk of infectious complications in SLE patients having mild-to-moderate disease activity, except for bronchitis. Baseline disease activity and organ damage did not impact the risk of infectious complications.

ObjectiveTo investigate the effects of belimumab (BEL) on systemic lupus erythematosus (SLE) mucocutaneous and vasculitis manifestations.MethodsThis post hoc, integrated Belimumab Summary of Lupus Efficacy (Be-SLE) analysis pooled data from five international Phase 3, randomized, placebo (PBO)-controlled BEL trials (BLISS-52 [NCT00424476; conducted in 2007-2009], BLISS-76 [NCT00410384; 2007-2009], BLISS-SC [NCT01484496; 2011-2015], North East Asia [NCT01345253; 2011-2015], EMBRACE [NCT01632241; 2013-2018]). Adults with active SLE and Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥6 (BLISS-52, BLISS-76) or ≥8 (BLISS-SC, North East Asia, EMBRACE), randomized to BEL (10 mg/kg/month intravenously or 200 mg/week subcutaneously) or PBO, plus standard therapy (ST) were included. Mucocutaneous and vasculitis manifestations (listed below) were measured (baseline and every 4 weeks) for 52 weeks using SELENA-SLEDAI and British Isles Lupus Assessment Group (BILAG).ResultsOf 3086 patients (BEL, n = 1869; PBO, n = 1217), 85% (BEL and PBO) by SELENA-SLEDAI and 58% (BEL) and 62% (PBO) by BILAG (moderate or severe activity) had mucocutaneous manifestations, and <10% had vasculitis at baseline. At Week 52, significantly more BEL-treated than PBO-treated patients demonstrated improvements in SELENA-SLEDAI (59% vs 49%; p < .0001) and BILAG (54% vs 43%; p < .0001) mucocutaneous domains. Significant differences between-treatment favored BEL at Week 52 for resolution of all SELENA-SLEDAI items (vasculitis, rash, alopecia, and mucosal ulcers), and nine of 20 BILAG items (mild maculopapular eruption, localized active discoid lesions, mild alopecia, small mucosal ulceration, malar erythema, subcutaneous nodules, swollen fingers, major cutaneous vasculitis including ulcers, and minor cutaneous vasculitis).ConclusionPatients with SLE treated with BEL plus ST experienced significant improvements in most mucocutaneous and vasculitis manifestations compared with patients receiving PBO plus ST. These data provide additional support for the use of BEL in SLE and show that it is associated with skin improvements.

Upon commencement of therapy for active disease, patients with systemic lupus erythematosus (SLE) show varying evolution regarding disease activity measures and patient-reported outcomes (PROs). Our objective was to identify disease evolution trajectories to gain a deeper understanding of SLE progression, ultimately improving future trial design.

Patients with ≥2 visits and available data on Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), British Isles Lupus Assessment Group (BILAG), Physician Global Assessment (PGA), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and glucocorticoid use were included in a post hoc analysis of four randomized controlled trials of belimumab (BLISS-52, BLISS-76, BLISS-SC, EMBRACE). Growth mixture modelling identified latent classes.

Among 2868 patients analysed, baseline median disease duration was 4.5 (interquartile range: 1.5-9.7) years and mean (±standard deviation) Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) 0.7 (±2.0), SLEDAI-2K 10.2 (±3.6), BILAG 17.0 (±7.8), PGA 1.5 (±0.5), FACIT-F 30.6 (±11.9) and prednisone dose 11.0 (±8.9) mg/day. In the initial model, glucocorticoid use and dose yielded high standard errors, indicating a weak link with the latent process. A refined model considered only clinical measures and FACIT-F, corrected for intervention and SDI; no other covariates improved the fit. Four classes best described disease evolution: highly active, responders; highly active, non-responders; moderately active, responders; moderately active, non-responders. Lupus Low Disease Activity State and Definitions of Remission in SLE remission attainment associated with latent classes.

By linking disease activity measures with PROs, we identified four distinct trajectories describing SLE evolution following the initiation of therapy. This classification could be valuable for personalizing treatment and guiding biological studies aimed at distinguishing patients with varying anticipated treatment responses, as no single clinical variable alone can predict disease progression.

To determine belimumab efficacy assessed using the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA) in patients with systemic lupus erythematosus (SLE) from phase III belimumab randomised controlled trials (RCTs).

A post hoc analysis was carried out on five RCTs in active adult SLE: four with intravenous (BLISS-52, BLISS-76, BLISS-NEA, EMBRACE) and one with subcutaneous belimumab (BLISS-SC). The 52-week landmark assessments were analysed across trials. Treatment response was defined according to BICLA criteria (BILAG improvement; no worsening of disease activity based on BILAG and Systemic Lupus Erythematosus Disease Activity Index-2K; no deterioration in Physician's Global Assessment ≥0.3 (scale: 0-3); no treatment failure).

A total of 3086 patients received belimumab (n=1869) or placebo (n=1217). BICLA response frequencies at week 52 were greater with belimumab vs placebo in BLISS-52 (OR (95% CI): 1.49 (1.05-2.12); p=0.024), BLISS-NEA (1.62 (1.12-2.33); p=0.010) and BLISS-SC (1.89 (1.39-2.57); p<0.001). A highly significant difference was observed in the pooled population (1.47 (1.25-1.72); p<0.001; adjusted for trial variance). Belimumab yielded greater BICLA response frequencies than placebo irrespective of baseline glucocorticoid dose (>7.5 or ≤7.5 mg/day of a prednisone equivalent), in patients with baseline SLEDAI-2K≥10 and in patients with positive anti-double-stranded (ds)DNA and/or low C3/C4 levels at baseline. Belimumab combined with anti-malarials yielded greater frequency of BICLA response attainment.

In this analysis of five RCTs evaluating belimumab in SLE, belimumab conferred superiority over placebo to yield BICLA response in the overall study population and in subgroups of patients with high global or serological activity at baseline. The benefit of belimumab was more prominent when combined with anti-malarials.

Systemic lupus erythematosus (SLE) is characterized by B cell dysregulation and expansion of atypical B cells that may correlate with disease manifestations and activity. This study investigated the impact of subcutaneous (sc) Belimumab (BLM) on the peripheral B cell compartment and on the functional properties of CD21low, T-bet+ and CD11c+ atypical B cells, in 21 active SLE patients over a 12-month period. At baseline, active SLE patients displayed reduced unswitched IgM memory B cells and expansion of atypical B cells, compared to healthy donors and to SLE patients in remission. sc BLM therapy promptly restored B cell homeostasis with a reduction of T-bet+ B cells, observed early in patients responsive to therapy. These findings highlight the pathogenic role of T-bet+ B cells in SLE disease and suggest their potential utility as biomarker of clinical response.

Deucravacitinib is an allosteric, selective tyrosine kinase 2 (TYK2) inhibitor that has demonstrated significant efficacy in the treatment of psoriasis. TYK2, a member of the Janus kinase (JAK) family, plays a critical role in intracellular signaling pathways for pro-inflammatory cytokines. Unlike traditional JAK inhibitors, which target active domains, deucravacitinib selectively binds to the pseudokinase domain of TYK2. This binding induces a conformational change that locks the enzyme in an inactive state, ensuring superior selectivity for TYK2 over JAK 1/2/3. This unique mechanism specifically inhibits key pro-inflammatory cytokines, including IL-12, IL-23, and type I interferons, critical in the pathogenesis of psoriasis and other immune-mediated diseases. As a result, deucravacitinib represents a promising option for targeted therapy in immune-mediated diseases and may reduce adverse events commonly associated with broader immunosuppressive treatments. Furthermore, its oral administration offers a convenient alternative to injectable biologics, potentially improving patient adherence and treatment satisfaction. This review highlights recent studies suggesting that deucravacitinib may also have therapeutic benefits in psoriatic arthritis, palmoplantar pustulosis, systemic lupus erythematosus, Sjogren's disease, and inflammatory bowel disease. Given its expanding therapeutic potential, deucravacitinib may provide a safer and more effective alternative to current therapies, offering a tailored approach to treatment.

To describe intravenous (IV) belimumab's clinical effectiveness in patients with systemic lupus erythematosus (SLE) in real-world practice in Saudi Arabia.

This retrospective, observational OBSErve study (GSK Study 215349) analyzed medical record data for adults with SLE receiving IV belimumab. Index date was the date of belimumab initiation. The primary endpoint was overall clinical response per physician judgement (categorized as worse, no improvement, improvement of <20%, 20-49%, 50-79%, ≥80%) at 6 months post-index. The secondary endpoints included changes from index in Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score and corticosteroid dose at 6 months post-index; and healthcare resource utilization (HCRU) 6 months pre- and post-index.

Of 47 patients enrolled, 44 patients completed ≥6 months of IV belimumab treatment and were included in the analysis. Most patients were female (91.5%) and the mean (standard deviation [SD]) age was 33.1 (8.1) years. At 6 months post-index, overall physician-assessed clinical improvements of ≥20% and ≥50% were reported for 97.7% (n=43) and 79.5% (n=35) of patients, respectively; 2.3% (n=1) of patients had no improvement, and no patient worsened. Mean SELENA-SLEDAI score decreased by 7.8 points during the 6 months post-index. Mean (SD) corticosteroid dose decreased from 10.2 (7.5) mg/day at index to 6.2 (3.4) mg/day at 6 months post-index. Reductions in unscheduled physician office and emergency room visits were observed during the post-index versus pre-index periods.

Real-world data from patients with SLE treated with IV belimumab in Saudi Arabia demonstrated clinical improvements and reductions in corticosteroid dose and HCRU. Although the low number of patients and lack of a control group limit interpretation, the similar findings to the other OBSErve studies support the effectiveness of belimumab for patients with SLE in Saudi Arabia.

Obexelimab is an investigational, bifunctional, non-depleting, humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit B cells, plasmablasts, and CD19-expressing plasma cells. In clinical trials, intravenous (IV) administration of obexelimab has been well-tolerated, and demonstrated clinical activity in patients with rheumatoid arthritis, systemic lupus erythematosus, and immunoglobulin G4-related disease. This study was performed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of obexelimab following subcutaneous (SC) administration, and compare PK/PD profiles between healthy Japanese and non-Japanese volunteers.

This was a Phase I, open-label, parallel group, multiple-dose study. Participants were randomized to five cohorts to receive three doses of obexelimab as 125 mg SC every 14 days (q14d), 250 mg SC q14d, 375 mg SC q14d, 250 mg IV q14d, and 125 mg SC every 7 days, then monitored during a 28-day safety follow-up period. PK/PD assessments were performed after the first and third doses.

A total of 50 healthy volunteers (25 Japanese and 25 non-Japanese) were enrolled and distributed evenly between dose cohorts. All SC dosing regimens were well-tolerated. Dose-proportional PK was observed following SC doses with a bioavailability of approximately 60%. No clinically meaningful differences in PK parameters were found between healthy Japanese and non-Japanese participants. Antidrug antibodies (ADA) were detected in 6/50 (12%) participants after dosing. ADA had no or minimal impact on PK in all six ADA positive participants. Near-complete CD19 receptor occupancy and an absolute B-cell count nadir of approximately 50% baseline levels were maintained for the duration of the study in both populations.

Obexelimab SC administration demonstrated favorable bioavailability, was well-tolerated, and showed no clinically meaningful ethnic differences in PK/PD. These results support further clinical development of SC obexelimab to treat B-cell mediated autoimmune diseases.

NCT02867098.

Despite some study demonstrated the effectiveness of telitacicept in patients with systemic lupus erythematosus (SLE), a noticeable gap exists in real-world data. This study aimed to examine the effectiveness and safety of telitacicept in patients with SLE in the real-world.

This retrospective study enrolled patients with SLE at the Tangdu Hospital from January 2022 to January 2023. These patients were administered telitacicept at 80 mg or 160 mg dosage. The observed outcomes were changes in the SLE Responder Index 4 (SRI-4), disease activity, renal function, and immunological indicators.

Sixty-one patients were enrolled, with 60 patients completed the 24-week follow-up, and 30 completed the 52-week. The SRI-4 response rates at 4, 12, 24, and 52 weeks were 52.5%, 67.2%, 75.4%, and 80.0%, respectively. No statistically differences were observed in the SRI-4 response rates between the 80 mg and 160 mg doses at any of the time points (all p > 0.05). By 52 weeks, the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index scores were significant decreased from baseline (p < 0.001), and complement 3 and 4 levels (p = 0.001), albumin levels (p = 0.004), and the overall change in glucocorticoid dosage (p < 0.001) were all significantly increased, with all showing significant changes over time (p < 0.001). During the study, 3 (4.9%) patients experienced infection, and 1 (1.6%) developed an allergy at the injection site.

Telitacicept exhibited a highly effective and favorable safety in patients with SLE, with improved renal and hematological manifestations and facilitated a reduction in glucocorticoid medication usage.

The pharmacokinetics (PK) of belimumab, a human immunoglobulin G1λ (IgG1λ) monoclonal antibody treatment for systemic lupus erythematosus (SLE), have been well reported. Clinical PK data in healthy participants and patients with SLE from Mainland China suggest lower-than-expected belimumab exposure. This study assessed inter-regional differences in belimumab exposure and efficacy via the exposure-response relationship to inform any dose-adjustment requirements.

Data from nine interventional belimumab studies in healthy participants and patients with SLE were used to update two-compartment PK models with first-order subcutaneous (SC) absorption, and a logistic regression model characterizing the 52-week SLE Responder Index (SRI) response in adult and paediatric patients with SLE. Covariates of belimumab PK and efficacy were identified using forward selection (P > .05) and backward elimination (P < .01). The models were evaluated using statistical tests and visual predictive checks.

Baseline fat-free mass was the most significant covariate affecting belimumab PK; baseline albumin and IgG concentrations were also PK covariates. After adjusting for covariates, Mainland Chinese patients had significantly higher observed belimumab clearance (28%) and central volume of distribution (20%) than other populations, leading to lower-than-expected exposures. Despite this, following the same dose, they were expected to have almost identical SRI response rates vs. other populations from the exposure-response analysis.

Belimumab 10 mg kg-1 intravenously every 4 weeks, or 200 mg SC every week, would achieve the maximum treatment effect for North East Asian patients with SLE (including Mainland Chinese) and similar responses to patients from other regions, despite lower reported exposures in Chinese patients.

The objective of this study was to identify predictors of renal flares in patients with SLE treated for active extra-renal disease.

Data from four clinical trials of belimumab in SLE (BLISS-52, NCT00424476; BLISS-76, NCT00410384; BLISS-NEA, NCT01345253; BLISS-SC, NCT01484496) were used. Patients were assigned to belimumab or placebo on top of standard therapy. We investigated the performance of predictors of renal flares through weeks 52-76 using proportional hazards regression analysis.

Of 3225 participants, 192 developed at least one renal flare during follow-up, with the first occurring after a median time of 197 days. Current/former renal involvement [hazards ratio (HR): 15.4; 95% CI: 8.3-28.2; P < 0.001], low serum albumin levels (HR 0.9; 95% CI: 0.8-0.9; P < 0.001), proteinuria (HR: 1.6; 95% CI: 1.5-1.7; P < 0.001), and low C3 levels (HR: 2.9; 95% CI: 2.1-4.1; P < 0.001) at baseline appeared robust determinants of impending renal flares. Anti-dsDNA positivity yielded an increased hazard for renal flares (HR: 2.1; 95% CI: 1.4-3.2; P < 0.001), which attenuated after adjustments. Anti-Sm positivity was associated with renal flares in the placebo (HR: 3.7; 95% CI: 2.0-6.9; P < 0.001) but not in the belimumab subgroup, whereas anti-ribosomal P positivity was associated with renal flares in the belimumab subgroup only (HR: 2.8; 95% CI: 1.5-5.0; P = 0.001).

A history of renal involvement, high baseline proteinuria, hypoalbuminaemia, and C3 consumption were robust determinants of impending renal flares. In addition to anti-dsDNA, anti-Sm and anti-ribosomal P protein antibody positivity may have value in surveillance of renal SLE.

The present study aimed to provide a comprehensive evaluation of the postmarketing safety of belimumab based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Adverse event (AE) reports in the FAERS database from January 2021 to December 2023 were extracted to perform the disproportionality analysis by calculating the reporting OR. The clinical characteristics and onset times of AEs were investigated. The differences across ages and regions in belimumab-related AEs were also explored.

A total of 4 974 201 AE reports were retrieved from the FAERS database, among which 9782 reports were related to belimumab. 485 positive safety signals related to belimumab were identified. In addition to the labelled AEs, such as depression and infections, new unexpected AEs, including product dose omission issue and inappropriate schedule of product administration, were identified. The median onset time of belimumab-related AEs was 75 days. Moreover, our analysis revealed frequently reported AEs in paediatric patients, such as systemic lupus erythematosus, and in adult patients, such as injection site pain. Additionally, AEs such as drug ineffective were commonly reported in patients of North America, Asia and Europe, while AEs, including an inappropriate schedule of product administration, had a high incidence in patients of South America.

The current study provides a valuable evaluation of the postmarketing safety of belimumab. Further studies are required to validate and confirm these findings. Clinicians should be vigilant regarding these potential AEs and pay more attention to the proper dosage regimen of belimumab in clinical practice.

The real-world effectiveness of intravenous (IV) belimumab in treating systemic lupus erythematosus (SLE) has been demonstrated in various countries through the OBSErve (evaluation Of use of Belimumab in clinical practice SEttings) program. Here we describe the clinical effectiveness of IV belimumab for treating SLE in real-world clinical practice in the Russian Federation.

In the retrospective, observational OBSErve Russia study (GSK Study 215349), eligible physicians enrolled adults with SLE receiving IV belimumab as part of their standard care. De-identified data were collected from patient medical records from September 2021 to March 2022. The primary outcome was the physician-assessed overall clinical response at 6 months post-index versus index (belimumab initiation) among patients receiving belimumab for ≥6 months. Other endpoints included change in Safety of Estrogens in Lupus Erythematosus National Assessment - SLE Disease Activity Index (SELENA-SLEDAI) score and glucocorticoid use.

Overall, 59 patients initiated IV belimumab, mainly due to the previous regimen not being effective and to decrease glucocorticoid use (76.3% each); 15.3% of patients started belimumab within the first year of SLE diagnosis. Only 13.6% of patients discontinued belimumab within the first 6 months, mainly due to loss to follow-up and loss of insurance/reimbursement. At 6 months post-index, among patients who completed ≥6 months of belimumab therapy (full analysis set, n = 53), 90.6% and 60.4% had an overall clinical improvement of ≥20% and ≥50%, respectively. Mean (standard deviation, SD) change in SELENA-SLEDAI score from index to 6 months post-index was -5.9 (4.3). Mean (SD) glucocorticoid dose decreased from 12.2 (7.3) mg/day at index to 8.6 (5.1) mg/day at 6 months post-index (n = 50).

Patients with SLE receiving IV belimumab for 6 months in real-world settings in the Russian Federation experienced overall clinical improvements and reductions in glucocorticoid use, which is an important long-term strategy of SLE treatment.

Cutaneous lupus erythematosus (CLE) is an autoimmune-mediated skin disease under the family of lupus erythematosus. Systemic immunosuppressants and topical treatments have been used to manage CLE; however, these treatments tend to be moderately efficacious and leave patients with unmet therapeutic needs. There is a need for medications that target pruritus, scarring, dyspigmentation, and other symptoms of chronic CLE that contribute to decreased quality of life. The introduction of new biologics and other systemic medications has expanded dermatologists' and rheumatologists' ability to manage CLE. This article discusses new pharmaceuticals and guidelines providing an updated overview of the clinical management of CLE.

To provide evidence-based clinical practice recommendations for managing Systemic Lupus Erythematosus (SLE) in Saudi Arabia.

This EULAR-adapted national guideline in which a multidisciplinary task force utilized the modified Delphi method to develop 31 clinical key questions. A systematic literature review was conducted to update the evidence since the EULAR publication. After reaching a consensus agreement, two rounds of voting and group discussion were conducted to generate consolidated recommendations/ statements.

A significant number of patients in Saudi Arabia experience delays in accessing rheumatologists, highlighting the significance of timely referral to SLE specialists or rheumatologists to ensure accurate diagnosis and prompt treatment. The primary goal of Glucocorticoid (GC) therapy in SLE patients is to establish disease control with a minimum dose and duration. Steroid-sparing agent utilization facilitates steroid-sparing goals. Hydroxychloroquine is recommended for all SLE patients, though physicians must carefully monitor toxicity and prioritize regular medication adherence assessment. SLE management during pregnancy starts from preconception time by assessing disease activity, major organ involvement, hypercoagulability status, and concomitant diseases that may negatively impact maternal and fetal outcomes. Multidisciplinary care with close monitoring may optimize both maternal and fetal outcomes. For patients with antiphospholipid antibodies, low-dose aspirin prophylaxis is recommended. Also, Long-term anticoagulant medications are fundamental to prevent secondary antiphospholipid syndrome due to high thrombosis recurrence.

This Saudi National Clinical Practice guidelines for SLE management provide evidence- based recommendations and guidance for healthcare providers in Saudi Arabia who are managing patients with SLE. These guidelines will help to standardize healthcare service, improve provider education, and perhaps lead to better treatment outcomes for SLE patients.

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.

A longitudinal retrospective multicenter 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.

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. A total of 27.2% of patients were in DORIS ≥50% of the visits and 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.

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.

Systemic lupus erythematosus (SLE) is a typical autoimmune disease; although severe disease and refractoriness to existing therapies are still experienced, the number of cases resistant to remission induction has decreased with the establishment of various therapies. However, improving long-term prognosis remains a challenge due to the unavoidable prolonged use of non-selective glucocorticoids. To investigate the additional effect of belimumab in the chronic phase, we included 28 of 46 patients with SLE who were initiated on belimumab between January 2018 and October 2022 for glucocorticoid reduction. The efficacy of tacrolimus and mycophenolate mofetil in combination with belimumab was also compared. In the stable chronic phase, the combination with belimumab improved the SLE Disease Activity Index and reduced glucocorticoid requirement. The tacrolimus with belimumab group was not significantly inferior to the mycophenolate mofetil with belimumab group and was effective in treatment and glucocorticoid sparing including cases at all phases of SLE. To improve the long-term prognosis of SLE, it is crucial to introduce highly selective biological agents and reduce glucocorticoids whenever possible. Belimumab is effective with or without hydroxychloroquine and Tac was effective as concomitant drugs.

BAFF, a vital B cell survival and differentiation factor, has three receptors: B-cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI) and BR3. Although B cells are greatly reduced in B6.Baff-/- (which harbour no BAFF) and B6.Br3-/- mice (which harbour supra-normal levels of BAFF), the distributions of B cell subsets and relationships between Foxp3+ and CD4+ cells in these mice differ. Using a large panel of B6 congenic knockout and/or transgenic mice, we demonstrate that (1) supra-normal levels of BAFF per se do not explain the phenotypic differences between B6.Baff-/- and B6.Br3-/- mice; (2) B cells are expanded in B6.Taci-/- mice, with preferential expansion of follicular (FO) B cells at the expense of CD19+CD21-/loCD23-/lo B cells but without the preferential expansion of Foxp3+ cells observed in B6 mice bearing a Baff transgene; (3) despite no expansion in total B cells, percentages of FO B cells and marginal zone B cells are higher and percentages of CD19+CD21-/loCD23-/lo B cells are lower in young B6.Bcma-/- mice, consistent with the inability of B6.Br3-/-.Taci-/- mice to recapitulate the B cell profile of B6.Baff-/- mice; and (4) percentages of Foxp3+ cells in B6.Br3-/-.Taci-/- mice are intermediate between those in B6.Br3-/- and B6.Taci-/- mice despite the B cell profile of B6.Br3-/-.Taci-/- mice strongly resembling that of B6.Br3-/- mice. Collectively, our findings point to a non-redundant role for each of the BAFF receptors in determining the ultimate lymphocyte profile of the host. This may have clinically relevant ramifications in that the degree that a candidate therapeutic agent blocks engagement of any given individual BAFF receptor may affect its clinical utility.

Although belimumab has been widely used in patients with systemic lupus erythematosus (SLE) globally, real-world safety data among Chinese patients are limited, particularly for children. This study assessed the safety and tolerability of belimumab in adult and paediatric patients with SLE in China in real-world clinical practice.

This Phase 4, multicentre, prospective, observational study enrolled patients prescribed intravenous belimumab by their physicians in tertiary hospitals, independent of a clinical study, during routine clinical visits between May 2021 and May 2022. Patients could have been receiving belimumab prior to enrolment. The primary objective was to describe the incidence of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs) and AEs of special interest (AESIs) over the 24-week follow-up period. Data were collected at enrolment and approximately 4, 12 and 24 weeks post-enrolment, during routine clinical visits. AEs, ADRs and SAEs were collected as independent events. The safety population comprised patients who received ≥1 dose of belimumab and completed ≥1 follow-up visit.

Overall, 417 patients were included in the analysis (safety population); 89.2% were female and mean (standard deviation) age was 35.5 (11.9) years. AEs were reported in 158 patients (37.9%) and were mostly mild (79.1%). The most common AEs were upper respiratory tract infections (n = 19, 4.6%) and hypokalaemia (n = 18, 4.3%; all mild). Among 22 patients (5.3%) with SAEs, four patients (1.0%) had drug-related SAEs (pneumonia, respiratory tract infection, gingivitis and decreased white blood cell and neutrophil count). ADRs were experienced by 25 patients (6.0%), most commonly urinary tract infections (n = 5, 1.2%). There were no fatal SAEs. AESIs occurred in 14 patients (3.4%), including infections of interest (n = 5, 1.2% all herpes zoster), serious selected psychiatric events (n = 3, 0.7%) and infusion-related systemic and anaphylactic reactions (n = 7, 1.7%). Of 14 paediatric patients enrolled, six experienced AEs, zero ADRs, two SAEs and one AESI.

Belimumab was generally well tolerated in adult and paediatric patients with SLE in this real-world setting in China, with no new safety signals identified. Future assessment of long-term belimumab safety in China beyond 24 weeks will extend this current body of evidence.

Belimumab was approved in the US in 2019 for children with Systemic lupus erythematosus (SLE), making it the only medicine that can treat SLE in both adults and children. The authors retrospectively investigated adverse events (AEs) by data-mining a self-reported database.

PRR, ROR, and BCPNN were used to assess the association between belimumab and AEs. The definition relied on system organ class (SOC) and peferred terms (PT) by the Medical Dictionary for Regulatory Activities (MedDRA).

A total of 15,316,605 AE reports were retrieved from the FAERS database, and 19,832 AE reports were identified after the data cleaning process. Based on the disproportionality analysis at the PT level, depressive (N = 420), ill-defined disorder (N = 304), injection site hemorrhage (N = 297), lupus nephritis (N = 198), live birth (N = 96) and proteinuria (N = 77) had relatively higher frequencies than other AEs, suggesting that these AEs are more likely to occur in the real world for patients taking belimumab.

This study explores valuable potential AEs of belimumab at the SOC and PT levels, respectively. To provide a reference for decision-making on belimumab, including its use in children, and to promote rational clinical dosing.

T follicular helper (Tfh) cells represent an important subset of CD4+ T cells that is crucial to the maturation and differentiation of B cells and the production of high-affinity antibodies. Because B cell activating-factor (BAFF), a vital B cell survival factor, is also crucial to B cell maturation and differentiation, we assessed the effects of BAFF on Tfh cell development and function. We demonstrated that deficiency of BAFF, but not of APRIL, markedly inhibited Tfh cell development, germinal center (GC) formation, and antigen-specific antibody production. The promoting effect of BAFF on Tfh cell development was dependent on expression of BR3 on T cells, and its promoting effect on GC formation was dependent on expression of BR3 on both T cells and B cells. BAFF directly promoted expression of the Tfh cell-characteristic genes via NF-κB signaling. This effect did need BR3 expression. Thus, BAFF not only has direct effects on B cells, but it also has direct effects on Tfh cell differentiation via engagement of BR3, which collectively promoted GC formation and production of high-affinity antibodies. This dual effect of BAFF on B cells and Tfh cells may help explain the clinical utility of BAFF antagonists in the management of certain autoimmune diseases.

Disease remission or low disease activity are key treatment targets for patients with systemic lupus erythematosus (SLE). Pivotal trials of belimumab were conducted before the introduction of these targets. In this study, we aimed to pool data across trials to assess attainment of remission and low disease activity in a large, racially and culturally diverse patient population with SLE.

In this integrated post-hoc analysis, we pooled data from five phase 3 trials of belimumab (BLISS-76 [NCT00410384], BLISS-52 [NCT00424476], BLISS-NEA [NCT01345253], BLISS-SC [NCT01484496], and EMBRACE [NCT01632241]), in patients with active, autoantibody-positive SLE. Patients were randomly assigned to receive belimumab (10 mg/kg per month intravenously or 200 mg per week subcutaneously) or placebo, plus standard therapy. The proportion of patients with Definitions of Remission in SLE (DORIS) remission and lupus low disease activity state (LLDAS) were analysed every 4 weeks from week 4 to week 52 for belimumab versus placebo, using modified Poisson regression adjusted for trial variance, in all patients and in subgroups per baseline SLE Disease Activity Index-2000 score (<10 or ≥10); anti-double stranded DNA positivity (yes or no); low complement 3 (C3) or C4 levels (yes or no); anti-dsDNA positivity or low C3 or C4 levels (yes and no); prednisone-equivalent dose (≤7·5 mg per day or >7·5 mg per day); antimalarial use (yes or no); and by race (Black African ancestry or African American, Asian, Indigenous American, or White).

Data for 3086 patients (1869 in the belimumab group and 1217 in the placebo group) were analysed. 2913 (94%) of 3086 patients were women and 173 (6%) were men, and the median age was 36 years (IQR 28-45). The proportion of patients with DORIS remission was significantly higher in the belimumab group than the placebo group at weeks 28, 48, and 52 (week 52: 148 [8%] of 1869 participants vs 68 [6%] of 1217 participants; risk ratio 1·51 [95% CI 1·15-1·99]; p=0·0055). The proportion of patients who attained LLDAS was higher in the belimumab group than the placebo group at weeks 8, 24, 32-52 (week 52: 322 [17%] of 1869 participants vs 125 [10%] of 1217 participants; 1·74 [1·44-2·12]; p<0·0001). A higher proportion of patients had DORIS remission at week 52 in the belimumab group than the placebo group among all baseline subgroups denoting high disease activity, with the exception of those on a prednisone-equivalent dose higher than 7·5 mg per day in whom there was no difference for DORIS remission with belimumab versus placebo. The proportion of patients with LLDAS was significantly higher among patients in the belimuab group than those who received placebo from week 44 in all baseline subgroups denoting high disease activity or earlier in some subgroups, and the differences were maintained at week 52.

In adults with active SLE, belimumab plus standard therapy yielded greater benefit than placebo plus standard therapy in attaining DORIS remission (for which low rates were attained in both groups) and LLDAS, with differences observed as early as week 28 for DORIS remission and week 8 for LLDAS.

Swedish Rheumatism Association, King Gustaf V's 80-year Foundation, Swedish Society of Medicine, Nyckelfonden, Professor Nanna Svartz Foundation, Ulla and Roland Gustafsson Foundation, Region Stockholm, and the Karolinska Institutet.

We assessed the contributions of B cell and T cell subsets to the disparate clinical outcomes in NZM.Baff-/- and NZM.Br3-/- mice.

We assessed in NZM wild-type, NZM.Baff-/-, and NZM.Br3-/- mice numbers and percentages of B cells and subsets, T cells and subsets, and in vivo proliferation and survival of forkhead box P3 (Foxp3)+ cells by fluorescence-activated cell sorting. Relationships between percentages of Foxp3+ cells and numbers of CD19+ and CD4+ cells were assessed by linear regressions.

In each age and sex cohort, percentages and numbers of CD19+ cells were similar in NZM.Baff-/- and NZM.Br3-/- mice. Percentages of CD3+ and CD4+ cells were greater in NZM.Br3-/- than in NZM.Baff-/- mice, with the CD4 to CD3 cell ratios being greater in NZM.Br3-/- than in NZM.Baff-/- mice and percentages of Foxp3+ cells in NZM.Br3-/- mice being lower than in NZM.Baff-/- mice. Percentages of Foxp3+ cells correlated positively with CD19+ cells in NZM.Baff-/- mice but negatively in NZM.Br3-/- mice. In vivo proliferation and survival of Foxp3+ cells were lower in NZM.Baff-/- mice than in NZM.Br3-/- mice.

Differences between NZM.Baff-/- and NZM.Br3-/- mice in Foxp3+ cells and their relationships with CD19+ cells may have more to do with their divergent clinical outcomes than do differences in numbers of B cells. These unexpected findings suggest that B cell activating factor (BAFF)-B cell maturation antigen (BCMA) or BAFF-Transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) interactions may help drive development of clinical systemic lupus erythematosus (SLE) even under conditions of considerable B cell depletion. Insufficient blocking of BAFF-BCMA and BAFF-TACI interactions may lie at the heart of incomplete clinical response to BAFF-targeting agents in human SLE.

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by dysregulated immune responses and autoantibody production, which affects multiple organs and varies in clinical presentation and disease severity. The development of SLE is intricate, encompassing dysregulation within the immune system, a collapse of immunological tolerance, genetic susceptibilities to the disease, and a variety of environmental factors that can act as triggers. This review provides a comprehensive discussion of the pathogenesis and treatment strategies of SLE and focuses on the progress and status of traditional and emerging treatment strategies for SLE. Traditional treatment strategies for SLE have mainly employed non-specific approaches, including cytotoxic and immunosuppressive drugs, antimalarials, glucocorticoids, and NSAIDs. These strategies are effective in mitigating the effects of the disease, but they are not a complete cure and are often accompanied by adverse reactions. Emerging targeted therapeutic drugs, on the other hand, aim to control and treat SLE by targeting B and T cells, inhibiting their activation and function, as well as the abnormal activation of the immune system. A deeper understanding of the pathogenesis of SLE and the exploration of new targeted treatment strategies are essential to advance the treatment of this complex autoimmune disease.

New treatments for systemic lupus erythematosus (SLE) aim to improve tolerability and disease activity control over standard of care (SoC) treatment. SoC typically includes daily glucocorticoid (GC) which carries a risk of organ damage over time. This study sought to develop natural history models to identify predictors of long-term outcomes with current SoC SLE treatment.

Generalized linear and parametric accelerated failure time survival models (GLM) and parametric accelerated failure time (AFT) survival models were designed to identify predictors of disease activity, flare rate, GC use, organ damage, and mortality beyond the first year of treatment in patients with SLE. Models were run using a longitudinal retrospective analysis of prospectively collected Toronto Lupus Cohort (TLC) study data, collected between 1997 and 2020. Covariates of clinical and statistical significance were selected by bivariate- then multi-variate regression to find the model of best fit.

Of the 1255 subjects included, 89 % were female 89 % and 65 % Caucasian. Mean follow-up was 10·5 years. At first visit, 51 % of patients had moderate-to-severe disease activity (SLEDAI-2 K score ≥ 6). Mean organ damage scores gradually increased over the years following diagnosis. Median survival of the cohort was ∼35 years from study entry. In the GLM models, SLEDAI-2 K yearly average, and average GC dose were key for predicting change in SLEDAI-2 K, GC use/ dose, and flare (any/rate). Together, adjusted mean SLEDAI-2 K and GC dose were shown to be predictors of mortality and damage in at least 9 of 12 organ systems considered.

These comprehensive, longitudinal, predictive models show that disease activity and GC use are significant predictors of organ damage and mortality in a patient population with predominantly moderate to severe SLE. This deepens understanding of SLE natural history and underscores the need for new treatment approaches that reduce disease activity and GC use with an aim to improve long-term SLE outcomes.

This study was funded by AstraZeneca.

This investigation leverages data derived from the United States Food and Drug Administration Adverse Event Reporting (FAERS) to real-world adverse reactions associated with Belimumab, with the intention of providing guidance for safe clinical pharmacotherapy.

Data encompassing adverse drug event (ADE) reports relating to Belimumab from Q1 2011 to Q4 2023 within the FAERS were extracted and analyzed using methodologies such as the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).

The study identified a total of 19 825 ADE reports where Belimumab was the primary suspect medication, with the United States constituting the majority of reporting countries (16 312 cases, or 82.28%). Patients aged 18 to 64.9 years accounted for the largest demographic (36.29%), while the proportion of female patients (77.91%) significantly surpassed that of male patients (5.03%). The analysis uncovered 184 unique Preferred Terms (PTs) across 21 System Organ Classes (SOCs). Following selection through ROR, the SOC signal strength was prioritized as follows: Systemic disorders and administration site conditions, infections and infestations, a variety of musculoskeletal and connective tissue disorders, and conditions related to pregnancy, puerperium, and the perinatal period. The top five PTs for ADE reports not included in the product's labeling were hypersensitivity reactions, immunosuppression, non-vascular diseases, herpes virus infections, and Sjögren's syndrome. The top five PTs for ADE signal strength not included in the labeling were disseminated cutaneous herpes zoster, herpes zoster meningitis, onycholysis, cyclothymic disorder, and mixed connective tissue disease.

Based on pharmacovigilance research utilizing the FAERS database, it is recommended that clinical monitoring of Bevacizumab should be intensified to support effective pharmaceutical care and ensure rational clinical medication use.

Substantial proportions of patients with SLE report poor health-related quality of life (HRQoL). Our objective was to investigate the impact of neuropsychiatric involvement (NP) in SLE on patient-reported outcomes.

We analysed data from four phase III trials (BLISS-52, BLISS-76, BLISS-SC, EMBRACE; N = 2968). The NPSLE group comprised individuals with NP-BILAG A/B/C/D or score in any descriptor of the NP-SLEDAI-2K at baseline (N = 350), while the non-NPSLE group consisted of patients with NP-BILAG E (N = 2618). HRQoL was assessed with the SF-36, EQ-5D-3L, and FACIT-F. Full health state (FHS) was defined as 'no problems' in all EQ-5D dimensions.

NPSLE patients reported lower scores in the SF-36 physical and mental component summary compared with the non-NPSLE population [mean (s.d.): 35.7 (9.1) vs 39.6 (9.6); P < 0.001 and 37.3 (12.1) vs 41.4 (11.0); P < 0.001, respectively]. NPSLE patients also exhibited impaired HRQoL in all EQ-5D dimensions compared with non-NPSLE patients (P < 0.05 for all). A substantially lower proportion of NPSLE patients experienced FHS in comparison with the non-NPSLE group (3.3% vs 14.5%; P < 0.001). NPSLE was associated with severe fatigue [23.8 (12.2) vs 31.5 (11.6); P < 0.001]. Notably, our findings revealed no discernible distinctions between active and inactive NPSLE patients with regard to SF-36, EQ-5D, FHS or FACIT-F scores.

NP in patients with SLE has a detrimental effect on HRQoL experience and is associated with severe fatigue, regardless of the degree of neuropsychiatric disease activity. Early intervention is warranted in NPSLE patients to enhance long-term HRQoL experience.

To investigate the association between neuropsychiatric systemic lupus erythematosus (NPSLE) and SLICC/ACR damage index (SDI) items, especially non-neuropsychiatric items.

Baseline data from five phase III trials (BLISS-52, BLISS-76, BLISS-SC, BLISS-NEA, EMBRACE) were analysed. NPSLE involvement was defined as NP BILAG A/B/C/D (n = 272); NP BILAG E denoted non-neuropsychiatric SLE (n = 3273). We employed multivariable logistic regression analysis adjusting for age, sex, disease duration, and ethnicity.

The median (IQR) and mean ± SD SDI scores were 0 (0-1) and 0.62 ± 1.09. Compared with the non-neuropsychiatric SLE group, NPSLE patients were more likely to develop damage (adjusted (a)OR = 2.86; 95% CI = 2.28-3.59). This held true also after suppression of the NP SDI items (aOR = 1.70; 95% CI = 1.36-2.12). Beyond the neuropsychiatric domain, NPSLE was associated with damage in the cardiovascular (aOR = 2.63; 95% CI = 1.75-3.95), musculoskeletal (aOR = 1.90; 95% CI = 1.43-2.52), and skin (aOR = 1.54; 95% CI = 1.06-2.22) SDI domains. Dissecting domains into items, NPSLE was associated with coronary artery disease (aOR = 3.08; 95% CI = 1.44-6.58), myocardial infraction (aOR = 3.11; 95% CI = 1.54-6.27), muscle atrophy (aOR = 3.34; 2.16-5.16), scarring alopecia (aOR = 1.79; 95% CI = 1.19-2.70), bowel infarction (aOR = 1.98; 95% CI = 1.20-3.26), retinopathy (aOR = 2.23; 95% CI = 1.15-4.32), and premature gonadal failure (aOR = 2.10; 95% CI = 1.11-3.90).

The intricate association between NPSLE and damage accrual extends beyond the nervous system to also comprise the musculoskeletal, skin, and cardiovascular organ systems.

Aim: Several studies have found subcutaneous (SC) and intravenous (IV) administration of similar drugs for long-lasting immunological and autoimmune diseases to have similar clinical effectiveness, meaning that what patients report they prefer is, or should be, a major factor in treatment choices. Therefore, it is important to systematically compile evidence regarding patient preferences, treatment satisfaction and health-related quality of life (HRQL) using SC or IV administration of the same drug. Materials & methods: PubMed database searches were run on 15 October 2021. Studies involving patients with experience of both home-based SC and hospital-based IV administration of immunoglobulins or biological therapies for the treatment of any autoimmune disease or primary immunodeficiencies (PIDs) were included. The outcomes assessed were patient preferences, treatment satisfaction and HRQL. Preference data were meta-analyzed using a random-effects model. Results: In total, 3504 citations were screened, and 46 publications describing 37 studies were included in the review. There was a strong overall preference for SC over IV administration, with similar results seen for PIDs and autoimmune diseases: PID, 80% (95% confidence interval [CI], 64-94%) preferred SC; autoimmune diseases, 83% (95% CI: 73-92%); overall, 82% (95% CI: 75-89%). The meta-analysis also found that 84% (95% CI: 75-92%) of patients preferred administration at home to treatment in hospital. Analysis of treatment satisfaction using the life quality index found consistently better treatment interference and treatment setting scores with SC administration than with IV administration. Conclusion: Compared with IV infusions in hospital, patients tend to prefer, to be more satisfied with and to report better HRQL with SC administration of the same drug at home, primarily due to the greater convenience. This study contributes to evidence-based care of patients with autoimmune diseases or PIDs.

The guanine nucleotide exchange factor (GEF) VAV1, a previously 'undruggable' protein integral to T/B lymphocyte antigen-receptor signaling, promotes actin polymerization, immunological synapse formation, T cell activation and differentiation, and cytokine production. With the development of novel modalities for targeting proteins, we hypothesize that interventions targeting VAV1 will have therapeutic potential in T and T/B cell-mediated autoimmune and chronic inflammatory diseases. This opinion is supported by recent CRISPR-Cas9 studies showing VAV1 as a key positive regulator of T cell receptor (TCR) activation and cytokine production in primary human CD4+ and CD8+ T cells; data demonstrating that loss/suppression of VAV1 regulates autoimmunity and inflammation; and promising preclinical data from T and T/B cell-mediated disease models of arthritis and colitis showing the effectiveness of selective VAV1 targeting via protein degradation.

Prompt disease control of flares in patients with systemic lupus erythematosus (SLE) is a priority in treatment strategy planning. However, the long-term dosage-related collateral effects of glucocorticoids (GCs) have pushed researchers towards the identification and utilization of novel biological agents that could both induce and maintain low disease activity and remission, especially in the context of lupus nephritis (LN). This scoping review aims at assessing the current evidence of the potential steroid-sparing effect of biologic therapies by reviewing phase II and phase III randomized, placebo-controlled trials involving SLE/LN patients. A scoping review of the literature was carried out in accordance with PRISMA-ScR recommendations. Risk of bias was assessed through the utilization of the Cochrane Collaboration's tool for randomized controlled trials (RCTs). Eight RCTs met the inclusion criteria and were included in this analysis (treatment drug, 7 belimumab; 1 anifrolumab). Four studies showed a definite steroid-sparing effect (treatment drug, 3 belimumab; 1 anifrolumab), while in the remaining four RCTs, the steroid-sparing effect was not observed. When focusing on phase III trials, the overall quality of the studies resulted fair or good considering the risk of bias. However, a degree of heterogeneity of steroid regimen protocol (considering initial dosage, tapering and rescue treatment allowance) was observed. While a growing body of evidence is supporting the safety and efficacy of biological treatment in SLE, the evidence on their steroid-sparing effect remains scattered. Future research needs to pursue the identification of precise SLE clusters of patients who would benefit most from a specific treatment protocol with a definite steroid-sparing effect.

The 2023 update of the EULAR recommendations for the management of systemic lupus erythematosus (SLE) faced several tasks: the newly approved medications anifrolumab and voclosporin as well as the additional approval of belimumab for lupus nephritis had to be conceptionally fitted into the management of SLE. Novel data on hydroxychloroquine and glucocorticoids, additional results for the treat-to-target goals remission and low disease activity and experience with respect to vaccinations and infections had to be considered. Additionally, EULAR specified a slightly modified structure. The update was further developed with 5 overarching principles and 13 recommendations. An SLE activity score is required for each patient visit. All SLE patients should receive hydroxychloroquine at a target dose of 5 mg/kg body weight. Glucocorticoids should only be used if necessary and reduced to not more than 5 mg prednisone equivalent daily in the long-term or, even better, tapered off. If the target of remission or low disease activity is not reached, methotrexate, azathioprine, mycophenolate and/or belimumab or anifrolumab should be used. For lupus nephritis, Euro-Lupus cyclophosphamide or mycophenolate are options for induction therapy and mycophenolate or azathioprine for maintenance. In the case of severe nephritis, the addition of belimumab or a calcineurin inhibitor (voclosporin or tacrolimus) should be considered. It is important that treatment should be continued for at least 3 years. This review article describes the details of the new recommendations against the background of relevant studies in recent years and classifies them in the clinical context.

Lupus nephritis remains the most frequent severe complication of systemic lupus erythematosus, leading to chronic renal impairment in 20 to 25% of cases. Current treatment is based on the combined use of immunosuppressive treatment and targeted biotherapies to optimize the chances of promptly obtaining and maintaining a complete renal response over the long term. The author discusses these recent advances.

Inflammatory rheumatic diseases are different pathologic conditions associated with a deregulated immune response, codified along a spectrum of disorders, with autoinflammatory and autoimmune diseases as two-end phenotypes of this continuum. Despite pathogenic differences, inflammatory rheumatic diseases are commonly managed with a limited number of immunosuppressive drugs, sometimes with partial evidence or transferring physicians' knowledge in different patients. In addition, several randomized clinical trials, enrolling these patients, did not meet the primary pre-established outcomes and these findings could be linked to the underlying molecular diversities along the spectrum of inflammatory rheumatic disorders. In fact, the resulting patient heterogeneity may be driven by differences in underlying molecular pathology also resulting in variable responses to immunosuppressive drugs. Thus, the identification of different clinical subsets may possibly overcome the major obstacles that limit the development more effective therapeutic strategies for these patients with inflammatory rheumatic diseases. This clinical heterogeneity could require a diverse therapeutic management to improve patient outcomes and increase the frequency of clinical remission. Therefore, the importance of better patient stratification and characterization is increasingly pointed out according to the precision medicine principles, also suggesting a new approach for disease treatment. In fact, based on a better proposed patient profiling, clinicians could more appropriately balance the therapeutic management. On these bases, we synthetized and discussed the available literature about the patient profiling in regard to therapy in the context of inflammatory rheumatic diseases, mainly focusing on randomized clinical trials. We provided an overview of the importance of a better stratification and characterization of the clinical heterogeneity of patients with inflammatory rheumatic diseases identifying this point as crucial in improving the management of these patients.