Isles Lupus Assessment Group Index Research Articles

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

BackgroundBelimumab 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. ObjectiveThe 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. MethodsSeveral 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). ResultsThe 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. ConclusionsThe 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.

Evaluation of the LFA-REAL clinician-reported outcome (ClinRO) and patient-reported outcome (PRO): prespecified analysis of the phase III ustekinumab trial in patients with SLE

ObjectiveThe Lupus Foundation of America Rapid Evaluation of Activity in Lupus (LFA-REAL) system is a novel and simple SLE disease activity instrument, consisting of a tandem clinician-reported (ClinRO) and patient-reported...

Effects of N-acetylcysteine on systemic lupus erythematosus disease activity and its associated complications: a randomized double-blind clinical trial study

BackgroundsN-acetylcysteine (NAC) has broadly been used as an anti-oxidant agent in various types of diseases. This study aimed to assess the effect of NAC on the systemic lupus erythematosus (SLE) disease activity and outcome.MethodsIn this randomized, double-blind clinical trial study, 80 SLE patients were recruited that were classified into two groups: 40 patients received NAC (1800 mg/day; 3 times per day with 8-h intervals) for 3 months and 40 patients as the control group received normal therapies. Laboratory measurements and disease activity based on the British Isles Lupus Assessment Group (BILAG) and SLE Disease Activity Index (SLEDAI) were determined before the initiation of treatment and after the study time period.ResultsA statistically significant decrease in BILAG (P= 0.023) and SLEDAI (P= 0.034) scores after receiving NAC for a 3-month period was observed. BILAG (P= 0.021) and SLEDAI (P= 0.030) scores were significantly lower in NAC-receiving patients compared to the control group after 3 months. The disease activity in each organ based on BILAG score after treatment indicated a significant decrease in the NAC group compared to the baseline level in general (P=0.018), mucocutaneous (P=0.003), neurological (P=0.015), musculoskeletal (P=0.048), cardiorespiratory (P=0.047), renal (P=0.025), and vascular (P=0.048) complications. Analysis indicated a significant increase in CH50 level in the NAC group after treatment compared to the baseline level (P=0.049). No adverse event was reported by the study subjects.ConclusionsIt appears that the administration of 1800 mg/day NAC to SLE patients can decrease the SLE disease activity and its complications.

Disease trajectory of SLE clinical endpoints and covariates affecting disease severity and probability of response: Analysis of pooled patient-level placebo (Standard-of-Care) data to enable model-informed drug development.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems. Many investigational agents have failed or shown only modest effects when added to standard of care (SoC) therapy in placebo-controlled trials, and only two therapies have been approved for SLE in the last 60 years. Clinical trial outcomes have shown discordance in drug effects between clinical endpoints. Herein, we characterized longitudinal disease activity in the SLE population and the sources of variability by developing a latent disease trajectory model for SLE component endpoints (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI], Physician's Global Assessment [PGA], British Isles Lupus Assessment Group Index [BILAG]) and composite endpoints (Systemic Lupus Erythematosus Responder Index [SRI], BILAG-based Composite Lupus Assessment [BICLA], and Lupus Low Disease Activity State [LLDAS]) using patient-level historical SoC data from nine phase II and III studies. Across all endpoints, in predictions up to 52 weeks from the final disease trajectory model, the following baseline covariates were associated with a greater decrease in SLE disease activity and higher response to placebo + SoC: Hispanic ethnicity from Central/South America, absence of hypocomplementemia, recent SLE diagnosis, and high baseline disease activity score using SLEDAI and BILAG separately. No discernible differences were observed in the trajectory of response to placebo + SoC across different SoC medications (antimalarial and immunosuppressant such as mycophenolate, methotrexate, and azathioprine). Across all endpoints, disease trajectory showed no difference in Asian versus non-Asian patients, supporting Asia-inclusive global SLE drug development. These results describe the first population approach to support a model-informed drug development framework in SLE.

Cardiac Safety of mRNA-Based Vaccines in Patients with Systemic Lupus Erythematosus and Lupus-like Disorders with a History of Myocarditis.

Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may trigger immune-mediated adverse events, including myocarditis. Evidence of vaccine safety in patients with rheumatic disorders and underlying autoimmune myocarditis is scarce. To address this issue, we studied 13 patients with systemic lupus erythematosus (SLE) and allied conditions with a history of myocarditis and receiving mRNA-based vaccines. Data about general and cardiac laboratory tests, treatment, and disease status were collected during routine consultations before and after the primary vaccination course and after each vaccine dose administration, while myocarditis symptoms were closely monitored. A significant increase in troponin levels from baseline was found after 13 (6–20) days from the first (p = 0.046) and 17 (4–29) days after the second dose (p = 0.013). Troponin levels progressively decreased within 3 (1–6) months in the absence of typical symptoms or signs of myocarditis. A significant increase in the constitutional domain of the British Isles Lupus Assessment Group (BILAG) index (p = 0.046) was observed in SLE patients. However, no patient needed any treatment change. mRNA-based anti-SARS-CoV-2 vaccines can apparently be safely administered to patients with SLE and lupus-like disorders with previous myocarditis despite potential subclinical and transient rises in cardiac damage markers.

Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) enables accurate and user-friendly definitions of clinical remission and categories of disease activity

ObjectivesThere is an unmet need for accurate and user-friendly definitions of systemic lupus erythematosus (SLE) disease activity and remission. We aimed to derive and validate the SLE Disease Activity Score...

Effect of nurse-led lifestyle intervention protocol on associated symptoms and self-efficacy among patients with systematic lupus erythematosus

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease. In addition to various clinical manifestations, it has spiritual, psycho-social and economic consequences. Aim: this study aimed to assess the effect of nurse-led lifestyle intervention protocol on associated symptoms and self-efficacy of patients with systematic lupus erythematosus. Design: A quasi-experimental pre/post-test one-group design. Setting: This study was conducted at Rheumatology unit, affiliated to Ain Shams University Hospitals. Subjects: A purposive non-probability/nonrandomized sample of 100 patients diagnosed with systemic lupus erythematosus. Tools: data were collected using two tools: I. Structured interview questionnaire for patients with systemic lupus erythematosus, II. General Self Efficacy Scale-GSE.III. British Isles Lupus Assessment Group (BILAG) Index. Results: there was a highly statistically significant difference between associated signs and symptoms of SLE pre and post implementation of life- style intervention protocol regarding treatment and self-management of SLE at p value (0.0001), there was a statistically significant difference regarding studied patients’ self-efficacy and patients’ lupus awareness pre and post life style intervention protocol implementation. Conclusion: the implementation of nurse-led lifestyle intervention protocol affected positively the lupus awareness, self-efficacy and improve the associated symptoms for patients with systematic lupus erythematosus. Recommendations: Continuous educational sessions to improve patients’ awareness, self-efficacy and improve the associated symptoms.

PMS43 Efficacy And Safety Of Pharmaceutical Treatments For Systemic Lupus Erythematosus (SLE): A Systematic Literature Review (SLR) Of Randomized Controlled Trials (RCTs)

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with systemic involvement causing widespread inflammation and tissue damage in affected organs. Limited success of available treatments requires novel therapies to address the high unmet need. This research aimed to identify efficacy and safety endpoints from RCTs assessing treatments for SLE. A SLR was conducted according to standard guidelines, including RCTs assessing treatments of SLE published in PubMed, Embase, and Cochrane (1999–2019). Outcomes of interest included any efficacy and safety endpoints. Of 14,083 initial hits, 54 publications were included. Among these, 46 reported efficacy outcomes, 42 described safety outcomes. Belimumab and anifrolumab were analyzed in 8 and 3 studies, respectively. Nine other investigational agents were tested in 2 respective studies. Mean patient age ranged 18.5–55.3 years; 93.1% were female. Mean disease duration from first diagnosis to RCT enrollment was 8.0 years. The most frequently reported efficacy endpoints were SLE responder index (SRI-4) (18/54), change in corticosteroid use (18/54), change in British Isles Lupus Assessment Group (BILAG) index (14/54), occurrence of flares (12/54) and BILAG-based Combined Lupus Assessment (BICLA) (10/54). The average difference in SRI-4 and BICLA between active interventions against placebo was 15% and 11% at Week 24 and 9% and 14% at Week 52, respectively. The rates of serious adverse events ranged 0%–40% across treatment arms. Death occurred in 15 RCTs (0.3%–11% for active treatments, ≤2% for placebo). This research revealed a high heterogeneity of study designs, population baseline characteristics and endpoint selection across RCTs in SLE. Efficacy levels of SLE treatments vary depending on the endpoint used, with overall high placebo rates observed. The revealed methodological challenges need to be addressed for indirect treatment comparisons to be able to inform formal value assessments of therapies aiming to improve the currently limited treatment success in SLE.

Efficacy and safety of rituximab for systemic lupus erythematosus treatment: a meta-analysis.

Given the inconsistency of previous studies and the newly emerging evidence, we decided to conduct a meta-analysis. The meta-analysis included 2 randomized controlled trials and 13 observational studies 742 patients in total. Qualified studies were properly searched from databases . Data were analyzed by the RevMan 5.3 software. Results were demonstrated as WMD , SMD and RR with 95% CIs, I2 and P value. we observed that a remarkable increase of complement C3 in the rituximab group than placebo group (WMDfixed= 7.67mg/dL, 95%CIs=-0.16~15.50, I2=0%, P=0.05). A significant increase of complement C4 was observed in the rituximab group than placebo group (WMDfixed=3.14mg/dL, 95%CIs=1.06~5.22, I2=0%, P=0.003). Notably decreased peripheral CD19+B cells in rituximab group than placebo group (WMDfixed=-117.93n/µl, 95%CIs=-172.94~-62.91, I2=0%, P<0.0001) in RCTs. Patients with severe or refractory SLE got more satisfactory efficacy results after receiving rituximab in observational studies, such as British Isles Lupus Assessment Group index score, SLE Disease Activity Index score, complement C3/C4, anti-dsDNA antibodies, peripheral CD19+B cells and so on. Safety profiles were no difference between rituximab and placebo groups. although the efficacy of rituximab is highly controversial for SLE, our study shows that rituximab presents a satisfying efficacy and safety for SLE.

Interleukin‐17 in urine and serum of patients with nephritis

Recent evidence suggests that interleukin-17 (IL-17) is involved in the pathogenesis of systemic lupus erythematosus (SLE) and it is a promising marker of disease activity in lupus nephritis (LN).1 IL-17 induces the expression of various pro-inflammatory cytokines and chemokines, which increase the influx of various leukocyte subpopulations and thus, causes severe inflammation. These inflammatory mediators enhance the involvement of various leukocyte subpopulations, which ultimately leads to damage.2, 3 Nordin et al published interesting data about IL-17 levels in 120 patients with SLE.4 The authors showed an increase in the levels of IL-17 in the serum and urine of patients and their correlations with British Isles Lupus Assessment Group and SLE Disease Activity Index scores, which is consistent with other studies.5, 6 But IL-17 was not a sensitive or specific marker of SLE activity. In addition, there was no correlations of IL-17 levels in urine or serum with the histological classes of LN. We also studied the levels of IL-17 in the urine and serum of patients with chronic glomerulonephritis (CGN). The levels of IL-17 in serum did not significantly differ from the levels in healthy individuals and did not depend on the activity of nephritis. On the contrary, the levels of IL-17A in the urine of patients with CGN were significantly higher at 3.05 (2.98-3.1) pg/mg creatinine (Cr) than that in healthy individuals 2.93 (2.92-2.94) pg/mg Cr The urinary IL-17A levels were not correlated with proteinuria (R2 = 0.21, P = .29) and serum albumin (R2 = 0.24, P = .21). These results indicate a connection between IL-17 levels in urine and inflammation of renal tissue in CGN patients. Also, IL-17 levels in the urine were significantly higher in the CGN patients with advanced interstitial fibrosis and a renal dysfunction with glomerular filtration rate less than 60 mL/min/1.73 m2 (2.97 [2.96-2.99] pg/mg Cr vs. 2.99 [2.98-3.00] pg/mg Cr in normal renal function, P < .05) regardless of histological forms. Currently, the role of IL-17 in fibrotic accumulation has been discussed. Severe fibrosis in murine radiation-induced lung disease was more pronounced with regard to reduction in Th1 cells in the presence of increased number of Th17 cells and higher levels IL-17.7 IL-6 can induce glomerulosclerosis and interstitial fibrosis in the kidney directly or through activation of IL-17.8 Changes in the Th17/Treg ratio may contribute to the development of advanced tissue fibrosis by transforming growth factor-β signaling through the activation of mitogen-activated protein kinases.9 Therefore, future research is needed to compare IL-17 levels in the urine with activity and sclerosis scores in the renal tissue and renal outcomes in LN.

Clinical and laboratory characteristics in juvenile-onset systemic lupus erythematosus across age groups.

BackgroundSystemic lupus erythematous (SLE) is a systemic autoimmune/inflammatory condition. Approximately 15–20% of patients develop symptoms before their 18th birthday and are diagnosed with juvenile-onset SLE (JSLE). Gender distribution, clinical presentation, disease courses and outcomes vary significantly between JSLE patients and individuals with adult-onset SLE. This study aimed to identify age-specific clinical and/or serological patterns in JSLE patients enrolled to the UK JSLE Cohort Study.MethodsPatient records were accessed and grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8–13 years) and adolescent (14–18 years). The presence of American College of Rheumatology (ACR) classification criteria, laboratory results, disease activity [British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores] and damage [Systemic Lupus International Collaborating Clinics (SLICC) damage index] were evaluated at diagnosis and last follow up.ResultsA total of 418 JSLE patients were included in this study: 43 (10.3%) with pre-pubertal disease onset; 240 (57.4%) with peri-pubertal onset and 135 (32.3%) were diagnosed during adolescence. At diagnosis, adolescent JSLE patients presented with a higher number of ACR criteria when compared with pre-pubertal and peri-pubertal patients [pBILAG2004 scores: 9(4–20] vs. 7(3–13] vs. 7(3–14], respectively, p = 0.015] with increased activity in the following BILAG domains: mucocutaneous (p = 0.025), musculoskeletal (p = 0.029), renal (p = 0.027) and cardiorespiratory (p = 0.001). Furthermore, adolescent JSLE patients were more frequently ANA-positive (p = 0.034) and exhibited higher anti-dsDNA titres (p = 0.001). Pre-pubertal individuals less frequently presented with leukopenia (p = 0.002), thrombocytopenia (p = 0.004) or low complement (p = 0.002) when compared with other age groups. No differences were identified in disease activity (pBILAG2004 score), damage (SLICC damage index) and the number of ACR criteria fulfilled at last follow up.ConclusionsDisease presentations and laboratory findings vary significantly between age groups within a national cohort of JSLE patients. Patients diagnosed during adolescence exhibit greater disease activity and “classic” autoantibody, immune cell and complement patterns when compared with younger patients. This supports the hypothesis that pathomechanisms may vary between patient age groups.

The additive effects of hydroxychloroquine to maintenance therapy with standard of care in patients with systemic lupus erythematosus.

In this retrospective study, the effect of hydroxychloroquine (HCQ) added to maintenance therapy according to the standard of care (SoC) was evaluated for 1year in 101 patients with systemic lupus erythematosus (SLE). The primary endpoint was the SLE Disease Activity Index (SLEDAI). The secondary endpoints were the British Isles Lupus Assessment Group index, serum complement activity (CH50) levels, anti-double-stranded DNA (dsDNA) antibody titer, concomitant corticosteroid (CS) dose, and Systemic Lupus International Collaborating Clinics (SLICC) damage index. These variables were compared between the SoC+HCQ (n=42) and SoC (n=59) groups. The SLEDAI improved from 2 (0, 6) to 0 (0, 4) in the SoC+HCQ group (P = .038) but significantly deteriorated from 1 (0, 4) to 2 (0, 8) in the SoC group (P = .033). CH50, anti-dsDNA antibody titer, concomitant CS dose, and SLICC damage index did not significantly change. The increase in the SLEDAI and concomitant CS dose after 1year were all significantly greater in the SoC group, and the proportion of patients with SLEDAI flare was significantly lower in the SoC+HCQ group (SoC+HCQ: 4.76% vs SoC: 25.4%, P=.006). Univariate logistic regression analyses identified HCQ as a predictive factor for no SLEDAI flare (P=.003, odds ratio 6.81, 95% confidence interval 1.77-45.00). The use of HCQ effectively improved SLEDAI scores and was a predictive factor for the prevention of SLEDAI flare. Therefore, HCQ may be considered a potential mainstay of maintenance therapy.

Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial

ObjectivesTo compare the efficacy to prevent flares of maintenance versus withdrawal of 5 mg/day prednisone in systemic lupus erythematosus (SLE) patients with clinically quiescent disease.MethodsA monocentric, 12-month, superiority, open-label, randomised...

Disease activity markers for SLE: is a little activity more helpful than none?

Systemic lupus erythematosus (SLE) is a heterogeneous collection of difficult-to-catalogue symptoms, physical findings, serological markers, and laboratory abnormalities manifested in varying degrees over time. In 1984, Urowitz et al1 proposed the first disease activity index—the LACC, or lupus activity criteria count. It took another 10 years to evolve consensus-derived activity indices, of which the British Isles Lupus Assessment Group (BILAG) and SLE Disease Activity Index (SLEDAI) stood out as being more useful and relevant than others.

Anti-CD22 epratuzumab for systemic lupus erythematosus: A systematic review and meta-analysis of randomized controlled trials.

Systemic lupus erythematosus (SLE) is a remarkable and challenging autoimmune disorder that is characterized by a broad range of clinical manifestations, such as flares and remissions. Recently, the humanized anti-CD22 antibody epratuzumab for SLE has been extensively studied. The aim of the present study was to perform a meta-analysis on the findings of associated randomized controlled trials in order to evaluate the effects of epratuzumab on SLE. Data from publications in PubMed, EMBASE and the Cochrane Library were collected up to March 2017. To calculate the risk ratio or standardized mean differences (SMDs) with 95% confidence intervals (CIs), a random effect model was applied when heterogeneity was significant and a fixed effect model was used when heterogeneity was negligible. All statistical tests were performed using Review Manager 5.3 software. A total of 1,921 participants in 4 studies (5 trials) that met the selection criteria were analyzed in this meta-analysis. Analyses of the BILAG-based Combined Lupus Assessment (BICLA) response and SLE Disease Activity Index 2000 (SLEDA-2K) score revealed that epratuzumab (720-3,600 mg) significantly improved the BICLA response (RR=1.09; 95% CI, 1.04 to 1.14) and decreased the SLEDA-2K score (SMD=-0.31; 95% CI, -0.67 to 0.06; P=0.10). While the British Isles Lupus Assessment Group index score was not significantly altered between the epratuzumab and control groups. For safety analyses, no statistically significant differences were identified between the two groups, which were proved by the pooled results (all P-values >0.05). These findings suggested that epratuzumab may be relatively safe and may have better therapeutic effectiveness than placebo control conditions in patients with SLE.

Safety and Tolerability of Omalizumab: A Randomized Clinical Trial of Humanized Anti-IgE Monoclonal Antibody in Systemic Lupus Erythematosus.

Autoreactive IgE antibodies have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). We hypothesize that omalizumab, a monoclonal antibody binding IgE, may improve SLE activity by reducing type I interferon (IFN) production by hampering plasmacytoid dendritic cells and basophil activation. This study was undertaken to assess the safety, tolerability, and clinical efficacy of omalizumab in mild to moderate SLE. Sixteen subjects with SLE and a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of ≥4 and elevated autoreactive IgE antibody levels were randomized to receive omalizumab or placebo (2:1) for 16 weeks, followed by 16 weeks of open-label treatment and a 4-week washout period. The SLEDAI-2K score, British Isles Lupus Assessment Group index (BILAG 2004) score, and physician's global assessment of disease activity were recorded at each visit. The type I IFN-induced gene signature was determined using quantitative polymerase chain reaction. Omalizumab was well tolerated with no allergic reactions, and mostly mild adverse events comparable to those experienced with placebo treatment. SLEDAI-2K scores improved in the omalizumab group compared to the placebo group at week 16 (P = 0.038), as well as during the open-label phase in subjects initially receiving placebo (P = 0.02). No worsening in BILAG scores or the physician's global assessment was detected. There was a trend toward a reduction in IFN gene signature in subjects treated with omalizumab (P = 0.11), especially in subjects with a high baseline IFN signature (P = 0.052). Our findings indicate that omalizumab is well tolerated in SLE and is associated with improvement in disease activity. Larger randomized clinical trials will be needed to assess the efficacy of omalizumab in patients with SLE.

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

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

Anifrolumab effects on rash and arthritis: impact of the type I interferon gene signature in the phase IIb MUSE study in patients with systemic lupus erythematosus

ObjectiveThis post hoc analysis compared anifrolumab 300 mg every 4 weeks with placebo on rash and arthritis measures with different stringency in patients with moderate to severe SLE (phase IIb;...

Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial

Patients with systemic lupus erythematosus have T-cell dysfunction that has been attributed to the activation of the mammalian target of rapamycin (mTOR). Rapamycin inhibits antigen-induced T-cell proliferation and has been developed as a medication under the generic designation of sirolimus. We assessed safety, tolerance, and efficacy of sirolimus in a prospective, biomarker-driven, open-label clinical trial. We did a single-arm, open-label, phase 1/2 trial of sirolimus in patients with active systemic lupus erythematosus disease unresponsive to, or intolerant of, conventional medications at the State University of New York Upstate Medical University (Syracuse, NY, USA). Eligible participants (aged ≥18 years) had active systemic lupus erythematosus fulfilling four or more of 11 diagnostic criteria defined by the American College of Rheumatology. We excluded patients with allergy or intolerance to sirolimus, patients with life-threatening manifestations of systemic lupus erythematosus, proteinuria, a urine protein to creatinine ratio higher than 0·5, anaemia, leucopenia, or thrombocytopenia. Patients received oral sirolimus at a starting dose of 2 mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/mL. Patients were treated with sirolimus for 12 months. Safety outcomes included tolerance as assessed by the occurrence of common side-effects. The primary efficacy endpoint was decrease in disease activity, assessed using the British Isles Lupus Assessment Group (BILAG) index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Blood samples of 56 matched healthy individuals were obtained as controls for immunobiological outcomes monitored at each visit. The primary efficacy endpoint was assessed in all patients who completed 12 months of treatment, and all patients who received at least one dose of treatment were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT00779194. Between March 9, 2009, and Dec 8, 2014, 43 patients were enrolled, three of whom did not meet eligibility criteria. 11 of the 40 eligible patients discontinued study treatment because of intolerance (n=2) or non-compliance (n=9). SLEDAI and BILAG disease activity scores were reduced during 12 months of treatment in 16 (55%) of 29 patients who completed treatment. Mean SLEDAI score decreased from 10·2 (SD 5·6) at enrolment to 4·8 (4·5) after 12 months of treatment (p<0·001) and the mean total BILAG index score decreased from 28·4 (12·4) at enrolment to 17·4 (10·7) after 12 months of treatment (p<0·001). The mean daily dose of prednisone required to control disease activity decreased from 23·7 mg (SD 9·6) to 7·2 mg (2·3; p<0·001) after 12 months of treatment. Sirolimus expanded CD4+CD25+FoxP3+ regulatory T cells and CD8+ memory T-cell populations and inhibited interleukin-4 and interleukin-17 production by CD4+ and CD4-CD8- double-negative T cells after 12 months. CD8+ memory T cells were selectively expanded in SRI-responders. Patient liver function and lymphocyte counts were unchanged. Although HDL-cholesterol (Z=-2·50, p=0·012), neutrophil counts (Z=-1·92, p=0·054), and haemoglobin (Z=-2·83, p=0·005) were moderately reduced during treatment, all changes occurred within a range that was considered safe. Platelet counts were slightly elevated during treatment (Z=2·06, p=0·0400). These data show that a progressive improvement in disease activity is associated with correction of pro-inflammatory T-cell lineage specification in patients with active systemic lupus erythematosus during 12 months of sirolimus treatment. Follow-up placebo-controlled clinical trials in diverse patient populations are warranted to further define the role of mTOR blockade in treatment of systemic lupus erythematosus. Pfizer, the National Institutes of Health, and the Central New York Community Foundation.

The Association Between Erythrocyte Sedimentation Rate, C3, C4, Anti-dsDNA Levels, and Renal Disease Activity, Based on BILAG Index in Females With Lupus Nephritis

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that involves many organs, such as the kidneys. Females are most affected and early detection of renal disease activity is very important for morbidity and mortality reduction. Objectives: The aim of this study was to determine the relationships between ESR, C3, C4, and anti-dsDNA levels and renal disease activity, based on renal components of the British Isles lupus assessment group (BILAG) index, in females with lupus nephritis (LN). Methods: This study retrospectively reviewed the medical files of 150 females, diagnosed as LN, who were on routine follow-up at Hafez hospital lupus clinic located in Shiraz, Southern part of Iran (during years 2014 to 2015). The BILAG index score was extracted and data was analyzed (α = 0.05). Results: In all 150 females with SLE, the mean (SD) age was 37.1 (10.6) years. There were significant relationships between BILAG index score and higher ESR level (P value = 0.01), positive anti-dsDNA (P value < 0.001) and low C4 level (P value = 0.003), statistically. However, the results were not significant for mild level of ESR and low level of C3. Conclusions: This study confirmed that the BILAG index score was a valuable predictive index for renal disease involvement in females with LN; thus the authors suggest clinicians to use this index for better LN management.