Discordant Perception of Disease Activity Between Providers and Adolescents with Systemic Lupus Erythematosus: A Cohort Study.

Discordance in perception of disease activity between adolescent patients with lupus and their providers may influence disease outcomes. We found that patients endorsed higher perceptions of disease activity than providers. Discordance was present at all levels of disease activity, particularly in patients with high activity, nephritis, and/or taking corticosteroids or mycophenolate mofetil.

Renal Response Outcomes of the EuroLupus and National Institutes of Health Cyclophosphamide Dosing Regimens in Childhood-Onset Proliferative Lupus Nephritis.

OBJECTIVE: We compared clinical characteristics and renal response in patients with childhood-onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen. METHODS: A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC. To evaluate the adjusted association between CYC regimen (EuroLupus vs NIH) and renal response over time, generalized estimating equations with a logit link were used. An interaction between time and CYC regimen was included, and a contrast between CYC regimens at 12 months was used to evaluate the primary outcome. RESULTS: One hundred forty-five patients (58 EuroLupus, 87 NIH) were included. EuroLupus patients were on average older at the start of current CYC therapy, had longer disease duration, and more commonly had relapsed or refractory LN compared with the NIH group. After multivariable adjustment, there was no significant association between CYC regimen and achieving complete renal response at 12 months (odds ratio [OR] of response for the EuroLupus regimen, reference NIH regimen: 0.76; 95% confidence interval [CI] 0.29-1.98). There was also no significant association between CYC regimen and achieving at least a partial renal response at 12 months (OR 1.35, 95% CI 0.57-3.19). CONCLUSION: Our study failed to demonstrate a benefit of the NIH regimen over the EuroLupus CYC regimen in childhood-onset proliferative LN. However, future prospective outcome studies are needed.

Recent Advances in Rib Plating.

Rib fractures are a common injury in blunt trauma and are associated with high morbidity and mortality. Recent advances in surgical stabilization of rib fractures (SSRF) have led to better patient outcomes for those with highly unstable complex rib fractures, as well as those with less severe injuries. This result has been due in part to the expansion of indications for repair, as well as the development of new hardware systems to address a variety of fracture patterns and injuries. This joint advancement of operator techniques, outcomes research, and industry development has brought SSRF to the forefront of rib fracture management and challenged non-operative paradigms. The future of repair is now shifting focus, as surgeons develop minimally invasive approaches and challenge manufacturers to develop new systems, instruments, and materials to address increasingly complex fracture patterns. These expansions promise to make SSRF an increasingly effective form of management for traumatic rib fractures.

B lymphocytes in treatment-naive paediatric patients with lupus are epigenetically distinct from healthy children.

BACKGROUND: SLE is likely triggered by gene-environment interactions. We have shown that most SLE-associated haplotypes encompass genomic regions enriched for epigenetic marks associated with enhancer function in lymphocytes, suggesting genetic risk is exerted through altered gene regulation. Data remain scarce on how epigenetic variance contributes to disease risk in paediatric SLE (pSLE). We aim to identify differences in epigenetically regulated chromatin architecture in treatment-naive patients with pSLE compared with healthy children. METHODS: Using the assay for transposase-accessible chromatin with sequencing (ATACseq), we surveyed open chromatin in 10 treatment-naive patients with pSLE, with at least moderate disease severity, and 5 healthy children. We investigated whether regions of open chromatin unique to patients with pSLE demonstrate enrichment for specific transcriptional regulators, using standard computational approaches to identify unique peaks and a false discovery rate of <0.05. Further analyses for histone modification enrichment and variant calling were performed using bioinformatics packages in R and Linux. RESULTS: We identified 30 139 differentially accessible regions (DAR) unique to pSLE B cells; 64.3% are more accessible in pSLE than healthy children. Many DAR are found in distal, intergenic regions and enriched for enhancer histone marks (p=0.027). B cells from adult patients with SLE contain more regions of inaccessible chromatin than those in pSLE. In pSLE B cells, 65.2% of the DAR are located within or near known SLE haplotypes. Further analysis revealed enrichment of transcription factor binding motifs within these DAR that may regulate genes involved in pro-inflammatory responses and cellular adhesion. CONCLUSIONS: We demonstrate an epigenetically distinct profile in pSLE B cells when compared with healthy children and adults with lupus, indicating that pSLE B cells are predisposed for disease onset/development. Increased chromatin accessibility in non-coding genomic regions controlling activation of inflammation suggest that transcriptional dysregulation by regulatory elements controlling B cell activation plays an important role in pSLE pathogenesis.

Non-Anastomotic Axillofemoral Bypass Disruption After Blunt Trauma Treated by Endovascular Approach.

Disruption in the non-anastomotic section of an axillofemoral bypass is a rare occurrence. In this report, we consider a patient who presented with a pseudoaneurysm in the non-anastomotic section of his axillofemoral bypass due to blunt trauma to the chest after a fall. Clinical presentation, management, treatment, and complications related to our case are discussed.

The safety of COVID-19 vaccination in immunocompromised children and young adults with immune-mediated inflammatory disease.

AIM: To assess safety of COVID-19 vaccination in paediatric patients with immune-mediated inflammatory disease (IMID). METHODS: Subjects of 5-21 years of age with IMID who received at least one COVID-19 vaccine completed electronic surveys after each vaccine to assess side effects within 1 week of vaccination, current medications and COVID-19 testing after vaccination. Charts were reviewed for COVID-19 polymerase chain reaction and IgG response to SARS-CoV-2 spike protein results and for disease flare during the study period. RESULTS: Among 190 enrolled subjects, 71% were female, with median age 17 (range 6-21) years. The most common diagnosis was juvenile idiopathic arthritis/rheumatoid arthritis (55%). 78% of subjects were taking immunosuppressive medication. At least one side effect was reported in 65% of subjects after any dose of the vaccine; with side effects in 38%, 53% and 55% of subjects after the first, second and third vaccine doses, respectively. The most common side effects were injection site pain (59%), fatigue (54%) and headache (39%). No anaphylaxis or myocarditis was reported. Three subjects (2%) experienced disease flare. CONCLUSION: In our cohort of paediatric patients with IMID, observed side effects were found to be mild and disease flare rates were found to be low following COVID-19 vaccination.

Virtual Access to Subspecialty Care.

Telehealth programs existed in many subspecialities before the COVID-19 pandemic, and the public health event motivated many subspecialties to reflect on how current technologies could be leveraged to benefit patient outcomes and increase health-care access. This article reviews the history and current state of telehealth access in many areas of subspecialty care. Primary care physicians (PCPs) may be unaware of the telehealth services and options local subspecialists offer. To best serve patients, PCPs could partner with subspecialists to develop processes to link patients to the right subspecialist at the right time and in the right visit type.

Adjuvant chemotherapy after neoadjuvant chemoradiation and proctectomy improves survival irrespective of pathologic response in rectal adenocarcinoma: a population-based cohort study.

BACKGROUND: This study sought to determine whether adjuvant chemotherapy (AC) compared to no AC (noAC) after neoadjuvant chemoradiation (CRT) and resection for rectal adenocarcinoma prolongs survival. Current guidelines from expert groups are conflicting, and data to support administering AC to patients who received neoadjuvant CRT are lacking. METHODS: A total of 19,867 patients met inclusion/exclusion criteria. Mean age was 58.6 ± 12.0 years, and 12,396 (62.4%) were males. Complete response (CR) was documented in 3801 (19.1%) patients and 8167 (41.1%) received AC. The cohort was stratified into pathological complete (pCR, N = 3801) and incomplete (pIR, N = 16,066) subgroups, and pIR further subcategorized into ypN0 (N = 10,191) and ypN + (N = 5875) subgroups. After propensity score matching, AC was associated with improved OS in the pCR subgroups (mean 139.1 ± 1.9 vs. 134.0 ± 2.2 months; p < 0.001), in pIR ypN0 subgroup (141.6 ± 1.5 vs. 129.9 ± 1.2 months, p < 0.001), and in pIR ypN + subgroup (155.9 ± 5.4 vs. 126.5 ± 7.6 months; p < 0.001). RESULTS: AC was associated with improved OS in patients who received neoadjuvant CRT followed by proctectomy for clinical stages II and III rectal adenocarcinoma. This effect persisted irrespective of pathological response status. CONCLUSIONS: AC following neoadjuvant CRT and surgery is associated with improved OS in patients with rectal adenocarcinoma. These findings warrant adoption of AC after neoadjuvant CRT and surgery for clinical stage II and III rectal adenocarcinoma.

Seroprevalence and clinical outcomes of SARS-CoV-2 in paediatric patients with rheumatic disease.

OBJECTIVES: Immunosuppressed paediatric patients with rheumatic disease (RD) may be at risk for severe or critical disease related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data remain scarce on coronavirus disease 2019 (COVID-19) outcomes in paediatric RD patients. The aim of this study was to determine the seroprevalence of SARS-CoV-2 IgG and to describe COVID-19 outcomes in immunosuppressed paediatric RD patients. METHODS: Patients diagnosed with RD before age 18 years and treated with at least one immunosuppressive medication for at least 3 months were enrolled from a tertiary paediatric rheumatology practice in New York and also underwent routine SARS-CoV-2 IgG testing from May to November 2020. A total of 571 patients were screened and 262 were enrolled. SARS-CoV-2 IgG-positive subjects were assessed for symptoms of COVID-19 infection. SARS-CoV-2 PCR results were recorded where available. Demographic, diagnostic, medication and outcome data were collected. RESULTS: Of 262 subjects (186 female), 35 (13%) were SARS-CoV-2 IgG positive; 17 (49%) had symptoms suggestive of COVID-19. Of the 17 patients who had SARS-CoV-2 PCR testing, 11 (65%) were PCR positive, 7 of whom were IgG positive. Most SARS-CoV-2 IgG-positive subjects were not PCR tested. The most common symptoms in IgG- and/or PCR-positive subjects were fever, fatigue and cough. No SARS-CoV-2 IgG- or PCR-positive subject developed severe or critical COVID-19 or required hospitalization. CONCLUSIONS: This is the first report of clinical outcomes of SARS-CoV-2 infection and seroprevalence of SARS-CoV-2 IgG in a large cohort of paediatric RD patients. Most SARS-CoV-2 IgG-positive subjects had no symptoms of COVID-19 infection. Symptomatic subjects all had mild COVID-19 symptoms, suggesting that the risk of severe or critical COVID-19 in immunosuppressed paediatric RD patients is minimal.

Differences in Healthcare Transition Views, Practices, and Barriers Among North American Pediatric Rheumatology Clinicians From 2010 to 2018.

OBJECTIVE: Since 2010, the rheumatology community has developed guidelines and tools to improve healthcare transition. In this study, we aimed to compare current transition practices and beliefs among Childhood Arthritis and Rheumatology Research Alliance (CARRA) rheumatology providers with transition practices from a provider survey published in 2010. METHODS: In 2018, CARRA members completed a 25-item online survey about healthcare transition. Got Transition's Current Assessment of Health Care Transition Activities was used to measure clinical transition processes on a scale of 1 (basic) to 4 (comprehensive). Bivariate analyses were used to compare 2010 and 2018 survey findings. RESULTS: Over half of CARRA members completed the survey (202/396), including pediatric rheumatologists, adult- and pediatric-trained rheumatologists, pediatric rheumatology fellows, and advanced practice providers. The most common target age to begin transition planning was 15-17 years (49%). Most providers transferred patients prior to age 21 years (75%). Few providers used the American College of Rheumatology transition tools (31%) or have a dedicated transition clinic (23%). Only 17% had a transition policy in place, and 63% did not consistently address healthcare transition with patients. When compared to the 2010 survey, improvement was noted in 3 of 12 transition barriers: availability of adult primary care providers, availability of adult rheumatologists, and pediatric staff transition knowledge and skills (P < 0.001 for each). Nevertheless, the mean current assessment score was < 2 for each measurement. CONCLUSION: This study demonstrates improvement in certain transition barriers and practices since 2010, although implementation of structured transition processes remains inconsistent.

Emerging B-Cell Therapies in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease of unknown etiology, whose hallmark is the production of autoantibodies. B cells are promising targets for novel SLE therapies. In 2011, belimumab (Benlysta®), a fully humanized monoclonal antibody inhibiting B-cell activation and proliferation, was the first medication in 50 years to be approved by the US Food and Drug Administration to treat adult SLE. This review discusses the current experience with B-cell-targeted therapies, including those targeting B-cell-surface antigens (rituximab, ocrelizumab, ofatumumab, obinutuzumab, obexelimab, epratuzumab, daratumumab), B-cell survival factors (belimumab, tabalumab, atacicept, blisibimod), or B-cell intracellular functions (ibrutinib, fenebrutinib, proteasome inhibitors), for the management of SLE. It focuses on ongoing clinical trials and real-world post-marketing use, where available, including their safety profiles, and concludes with our recommendations for B-cell-centric approaches to the management of SLE.

Performance and psychometric properties of lupus impact tracker in assessing patient-reported outcomes in pediatric lupus: Report from a pilot study.

OBJECTIVE: To evaluate the reliability, validity, feasibility and psychometric performance of the Lupus Impact Tracker (LIT) as a patient reported outcome (PRO) measure tool in pediatric systemic lupus erythematosus (pSLE). METHODS: This is a prospective, observational, pilot study where patients aged between 12 and 25 years, fulfilling the 1997 ACR classification criteria for SLE, were enrolled. Over 3 consecutive, routine, clinical visits, the patients completed the LIT alongside the Patient-Reported Outcomes Measurement Information System-Short Forms (PROMIS-SFs), Childhood Health Assessment Questionnaire (CHAQ). Rheumatologists completed the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC-ACR) Damage Index. Demographic, clinical and laboratory data were also collected. RESULTS: Of 46 patients enrolled, 38 patients completed 2 visits and 31 completed all 3 visits. Seventy-eight percent were female, 33% African American, 28% Asian, 15% Caucasian and 17% Hispanic. The mean (SD) age was 17.2 (2.7) years, with a mean (SD) disease duration of 4.6 (3.1) years. The mean (SD) SLEDAI-2K at enrollment was 3.54 (2.96). In the 38 patients who completed two or more visits, intra-class correlation coefficient and Cronbach alpha were calculated to be 0.70 and 0.91 respectively, signifying good reliability of LIT. The LIT showed positive correlation with CHAQ-Disability Index and majority of the PROMIS-SFs parameters. Construct validity was established against clinical disease activity (SLEDAI-2K). CONCLUSION: The preliminary results indicate that the LIT is a reliable and valid instrument to capture PRO in p-SLE. Prospective validation with a larger, multicenter cohort is the next step.

Management of Pediatric Systemic Lupus Erythematosus: Focus on Belimumab.

Belimumab (Benlysta®) is a fully humanized monoclonal antibody that inhibits B lymphocyte stimulator (BLyS, also known as B cell-activating factor of the tumor necrosis factor family) and was approved by the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency for the treatment of autoantibody-positive systemic lupus erythematosus (SLE) in adults with moderate disease activity. Belimumab was recently FDA approved for use in children with SLE between 5 and 17 years of age. This review discusses the key findings of the belimumab phase III trials in adult SLE (via intravenous and subcutaneous administrations), phase II trial in pediatric SLE (intravenous administration), and post hoc analyses. It also evaluates the current clinical trials of belimumab in specific SLE disease states and highlights the safety profile of belimumab. It discusses the clinical post-marketing use of belimumab in adults and children with SLE and concludes with our recommendations for the use of belimumab to treat pediatric SLE, including a look to the future with increased real-world use in children with SLE.

Prevalence of progressive multifocal leukoencephalopathy (PML) in adults and children with systemic lupus erythematosus.

OBJECTIVE: To define the risk of progressive multifocal leukoencephalopathy (PML) in SLE. METHODS: This is a retrospective observational study to evaluate PML cases in patients with SLE admitted to two large academic hospitals. Using electronic medical record (EMR) data, International Classification of Diseases (ICD) codes identified PML cases among patients with SLE, rheumatoid arthritis (RA) (controls), had renal transplant and with HIV. Medication exposure was reviewed. RESULTS: A total of 5409 Columbia University Medical Center (CUMC) patients and 2046 Northwell Health patients were identified using one ICD code for SLE. Of 7455 patients, three had an ICD code for PML. On EMR review, however, PML was substantiated in only one fatal SLE case with significant immunosuppressant use and severe lymphopenia (<0.5 cells x 109/L); one patient was evaluated for PML but cerebrospinal fluid (CSF) was negative for JC virus and improved with treatment of central nervous system (CNS) lupus. EMR data were very limited for the third patient and diagnosis could not be confirmed. None of the 13 342 patients with RA ICD codes had PML. Of the 5409 patients with an SLE ICD code at CUMC, 212 also had a renal transplant ICD code, and 83 had concomitant HIV/AIDS. Based on inpatient pharmacy records of 5409 hospitalised patients at CUMC, 59.2% were treated with steroids, and 16.09% with immunosuppressants (7.76% mycophenolate, 3.42% cyclophosphamide, 2.88% azathioprine and 2.03% rituximab). No patients with paediatric SLE (pSLE) (n=538) had PML. The combined prevalence of PML in hospitalised patients with SLE at the two hospitals was 13-27/100 000 patients. CONCLUSION: Among 7455 adult patients with SLE ICD codes, there were two PML cases, with only one confirmed case associated with severe lymphopenia and immunosuppressants, corresponding to a prevalence of 13-27 per 100 000 patients. No PML cases in pSLE were found. A high index of suspicion in patients with SLE and CNS manifestations is required for the prompt diagnosis of PML.

Validation of the 2019 European League Against Rheumatism/American College of Rheumatology Criteria Compared to the 1997 American College of Rheumatology Criteria and the 2012 Systemic Lupus International Collaborating Clinics Criteria in Pediatric Systemic Lupus Erythematosus.

OBJECTIVE: Different classification criteria for systemic lupus erythematosus (SLE) have been proposed for many years. The most widely used and accepted criteria has been the 1997 American College of Rheumatology (ACR) criteria. In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) criteria were published in an attempt to improve the clinical relevance of SLE criteria. In 2017, weighted criteria were proposed that included entry criteria, something the 1997 ACR and the 2012 SLICC criteria did not identify. The aim of the present study was to validate the 2017 weighted criteria, the 1997 ACR criteria, and the 2012 SLICC criteria and compare the sensitivities and specificities in pediatric SLE. METHODS: For the past 15 years, retrospective chart review of patients diagnosed with SLE before age 19 years was conducted. The controls were patients referred for serologies positive for antinuclear antibodies but did not fulfill criteria for diagnosis of SLE at the initial visit or were diagnosed with another autoimmune disease. The 3 classification criteria sets were applied to these patients and compared against a gold standard of physician diagnosis. RESULTS: A total of 156 patients were diagnosed with SLE. The sensitivity for the 2017 weighted criteria was 0.974 (95% confidence interval [95% CI] 0.936-0.993) and the specificity was 0.984 (95% CI 0.966-0.994). The sensitivity for the 1997 ACR criteria was 0.872 (95% CI 0.809-0.920) and the specificity was 1.00 (95% CI 0.990-1.000). The sensitivity for the 2012 SLICC criteria was 0.974 (95% CI 0.936-0.993) and the specificity was 0.997 (95% CI 0.985-1.000). CONCLUSION: The 2017 weighted criteria and the 2012 SLICC criteria were more sensitive than the 1997 ACR criteria. There were no significant differences in sensitivity and specificity between the 2012 SLICC and the 2017 weighted criteria.

Chromatin landscapes and genetic risk in systemic lupus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a multi-system, complex disease in which the environment interacts with inherited genes to produce broad phenotypes with inter-individual variability. Of 46 single nucleotide polymorphisms (SNPs) shown to confer genetic risk for SLE in recent genome-wide association studies, 30 lie within noncoding regions of the human genome. We therefore sought to identify and describe the functional elements (aside from genes) located within these regions of interest. METHODS: We used chromatin immunoprecipitation followed by sequencing to identify epigenetic marks associated with enhancer function in adult neutrophils to determine whether enhancer-associated histone marks were enriched within the linkage disequilibrium (LD) blocks encompassing the 46 SNPs of interest. We also interrogated available data in Roadmap Epigenomics for CD4+ T cells and CD19+ B cells to identify these same elements in lymphoid cells. RESULTS: All three cell types demonstrated enrichment of enhancer-associated histone marks compared with genomic background within LD blocks encoded by SLE-associated SNPs. In addition, within the promoter regions of these LD blocks, all three cell types demonstrated enrichment for transcription factor binding sites above genomic background. In CD19+ B cells, all but one of the LD blocks of interest were also enriched for enhancer-associated histone marks. CONCLUSIONS: Much of the genetic risk for SLE lies within or near genomic regions of disease-relevant cells that are enriched for epigenetic marks associated with enhancer function. Elucidating the specific roles of these noncoding elements within these cell-type-specific genomes will be crucial to our understanding of SLE pathogenesis.

The Crossmatch/Issue Ratio: Use of a Novel Quality Indicator and Results of an International Survey on RBC Crossmatching and Issuing Practices.

OBJECTIVES: To understand the worldwide scope of RBC crossmatching and issuing practices and measure efficiency using a novel quality indicator, the crossmatch/issue (C/I) ratio. METHODS: An electronic survey was disseminated to hospital transfusion services collecting details about RBC crossmatching and issuing practices. Respondents were asked to enumerate the number of RBCs crossmatched and issued at their institutions during the 2014 calendar year to calculate the C/I ratio. RESULTS: Fifty-two survey responses were received, mostly from North American transfusion services (28/52, 54%). The electronic crossmatch was the most common technique (n = 29), and most respondents performed the crossmatch at the time that an order for RBCs was received in the transfusion service (even if an order to issue the RBCs was not received). Data to calculate the C/I ratio were supplied by 22 respondents, and the mean ± SD was 1.30 ± 0.34. There was no difference in C/I ratios between services that use the electronic or serologic crossmatch techniques (P = .49). The ratio was the same at the four sites that crossmatch RBCs at the time of issue compared with the time of order receipt (mean ± SD, 1.11 ± 0.09 vs. 1.35 ± 0.36, respectively; P = .19). CONCLUSIONS: Electronic crossmatching is common, and the C/I ratio can be an indicator of efficiency.

Use of Glucuronidated Mycophenolic Acid Levels for Therapeutic Monitoring in Pediatric Lupus Nephritis Patients.

BACKGROUND/OBJECTIVES: Mycophenolate mofetil (MMF) is used to treat pediatric-onset lupus nephritis (pLN). Data are equivocal on the use of plasma mycophenolic acid (MPA) levels as a measure of efficacy and predictor of therapeutic outcomes in pLN. Glucuronidated MPA (MPA-G) is an inactive metabolite that is a marker of adequate absorption and normal metabolism of MMF. We evaluated the use of MPA and MPA-G levels in routine care of pLN. METHODS: This was a retrospective study of pLN patients treated with MMF dosed at 600 mg/m. Clinical renal remission (CR) was defined as proteinuria of less than 500 mg/24 h. Midinterval MPA and MPA-G plasma levels were drawn during routine follow-up, approximately 6 hours after the previous dose of MMF. Steady-state levels of MPA were calculated using pharmacokinetics and compared with routine midinterval plasma MPA levels. RESULTS: Seventeen pLN patients treated with MMF had MPA and MPA-G levels. Eleven patients were in CR; 6 were not in CR at the time of evaluation and had not responded to MMF after more than 3 months of therapy. The mean MPA level for patients in CR was 3.26 ± 2.02 µg/mL compared with 3.02 ± 1.76 µg/mL for patients not in CR. Three patients in CR did not have detectable levels of MPA. Calculated steady-state levels of MPA did not reflect the observed levels. Glucuronidated MPA levels were therapeutic (44.2 ± 26.7 µg/mL) in patients in CR, but low (29.88 ± 22 µg/mL) in patients not in CR (not statistically significant). CONCLUSIONS: Midinterval plasma levels of MPA do not reflect predicted steady-state levels in pLN and do not correlate with clinical response. Midinterval plasma levels of MPA-G indicate adequate absorption and may correlate better with clinical pLN activity.

Safety and Efficacy of Belimumab to Treat Systemic Lupus Erythematosus in Academic Clinical Practices.

OBJECTIVE: To evaluate the use and efficacy of belimumab in academic practices. Belimumab is a human monoclonal antibody that inhibits soluble B lymphocyte stimulator and has been approved for the treatment of adults with systemic lupus erythematosus (SLE). METHODS: Invitations to participate and complete a 1-page questionnaire for each patient prescribed belimumab were sent to 16 physicians experienced in SLE phase III clinical trials. The outcome was defined as the physician's impression of improvement in the initial manifestation(s) being treated without worsening in other organ systems. RESULTS: Of 195 patients treated with belimumab at 10 academic centers, 96% were taking background medications for SLE at initiation of belimumab, with 74% taking corticosteroids. The main indications for initiation of belimumab were arthritis, rash, and/or worsening serologic activity, with 30% of patients unable to taper corticosteroids. Of the 120 patients taking belimumab for at least 6 months, 51% responded clinically and 67% had ≥ 25% improvement in laboratory values. While numbers are limited, black patients showed improvement at 6 months. In a subset of 39 patients with childhood-onset SLE, 65% responded favorably at 6 months, and 35% discontinued corticosteroids. CONCLUSION: Our data demonstrate favorable clinical and laboratory outcomes in patients with SLE at 6 months across all racial and ethnic groups, with similar improvement seen among patients with childhood-onset SLE.

Belimumab in systemic lupus erythematosus: a perspective review.

Belimumab (Benlysta(®)) is a fully humanized monoclonal antibody that inhibits B-lymphocyte stimulator (also known as B cell activating factor of the tumor necrosis factor family) and was approved by the US Food and Drug Administration and the European Medicines Evaluation Agency for treatment of autoantibody-positive systemic lupus erythematosus (SLE) in adults. This review discusses the key findings of the phase III trials, post hoc analyses, and real-world postmarketing use of belimumab in the routine care of SLE patients. It also highlights the safety profile of belimumab and gives insight into its potential use to treat childhood-onset SLE. It concludes with a discussion of the current clinical trials investigating belimumab in specific SLE disease states and a look to the future with novel targeted B-cell therapies.