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Objective: Given fibromyalgia (FM) frequently co‐occurs with autoimmune disease, this study was initiated to objectively evaluate FM in a multiracial/ethnic cohort of patients with systemic lupus erythematosus (SLE). Methods: Patients with SLE were screened for FM using the 2016 FM classification criteria during an in‐person rheumatologist visit. We evaluated hybrid Safety of Estrogens in Lupus National Assessment (SELENA)‐SLE Disease Activity Index (SLEDAI) scores, SLE classification criteria, and Systemic Lupus International Collaborating Clinics damage index. We compared patients with and without FM and if differences were present, compared patients with FM with patients with non‐FM related chronic pain. Results: 316 patients with SLE completed the FM questionnaire. 55 (17.4%) met criteria for FM. The racial composition of patients with FM differed from those without FM (P = 0.023), driven by fewer Asian patients having FM. There was no difference in SLE disease duration, SELENA‐SLEDAI score, or active serologies. There was more active arthritis in the FM group (16.4%) versus the non‐FM group (1.9%) (P < 0.001). The Widespread Pain Index and Symptom Severity Score did not correlate with degree of SLE activity (r = −0.016; 0.107) among patients with FM or non‐FM chronic pain (r = 0.009; −0.024). Regarding criteria, patients with FM had less nephritis and more malar rash. Systemic Lupus International Collaborating Clinics damage index did not differ between groups. Conclusion: Except for arthritis, patients with SLE with FM are not otherwise clinically or serologically distinguishable from those without FM, and Widespread Pain Index and Symptom Severity Score indices do not correlate with SLEDAI. These observations support the importance of further understanding the underlying biology of FM in SLE. [ABSTRACT FROM AUTHOR]

Objective: AURORA 2 evaluated the long‐term safety, tolerability, and efficacy of voclosporin compared to placebo in patients with lupus nephritis (LN) receiving an additional two years of treatment following completion of the one‐year AURORA 1 study. Methods: Enrolled patients continued their double‐blinded treatment of voclosporin or placebo randomly assigned in AURORA 1, in combination with mycophenolate mofetil and low‐dose glucocorticoids. The primary objective was safety assessed with adverse events (AEs) and biochemical and hematological assessments. Efficacy was measured by renal response. Results: A total of 216 patients enrolled in AURORA 2. Treatment was well tolerated with 86.1% completing the study and no unexpected safety signals. AEs occurred in 86% and 80% of patients in the voclosporin and control groups, respectively, with an AE profile similar to that seen in AURORA 1, albeit with reduced frequency. Investigator reported AEs of both glomerular filtration rate (GFR) decrease and hypertension occurred more frequently in the voclosporin than the control group (10.3% vs 5.0%, and 8.6% vs 7.0%, respectively). Mean corrected estimated GFR (eGFR) was within the normal range and stable in both treatment groups. eGFR slope over the two‐year period was −0.2 mL/min/1.73 m2 (95% confidence interval [CI] −3.0 to 2.7) in the voclosporin group and −5.4 mL/min/1.73 m2 (95% CI −8.4 to −2.3) in the control group. Improved proteinuria persisted across three years of treatment, leading to more frequent complete renal responses in patients treated with voclosporin (50.9% vs 39.0%; odds ratio 1.74; 95% CI 1.00–3.03). Conclusion: Data demonstrate the safety and efficacy of long‐term voclosporin treatment over three years of follow‐up in patients with LN. [ABSTRACT FROM AUTHOR]

Objective: Enrollment of patients of Black African ancestry with systemic lupus erythematosus (SLE) in phase II and phase III of the belimumab trials was not reflective of the racial distribution observed in the lupus population. This study was undertaken to assess the efficacy and safety of intravenous (IV) belimumab plus standard therapy in patients of self‐identified Black race. Methods: EMBRACE (GSK Study BEL115471; ClinicalTrials.gov identifier: NCT01632241) was a 52‐week multicenter, double‐blind, placebo‐controlled trial in adults of self‐identified Black race with active SLE who received monthly belimumab 10 mg/kg IV, or placebo, plus standard therapy. The optional 26‐week open‐label extension phase included patients who completed the double‐blind phase. The primary end point of the study was SLE Responder Index (SRI) response rate at week 52 with modified proteinuria scoring adapted from the SLE Disease Activity Index 2000 (SLEDAI‐2K) (SRI–SLEDAI‐2K). Key secondary end points included SRI response rate at week 52, time to first severe SLE flare, and reductions in prednisone dose. Results: The modified intent‐to‐treat population comprised 448 patients, of whom 96.9% were women and the mean ± SD age was 38.8 ± 11.42 years. The primary end point (improvement in the SRI–SLEDAI‐2K response rate at week 52) was not achieved (belimumab 48.7%, placebo 41.6%; odds ratio 1.40 [95% confidence interval 0.93, 2.11], P = 0.1068); however, numerical improvements favoring belimumab were observed, in which the SRI–SLEDAI‐2K response rates were higher in those who received belimumab compared with those who received placebo, especially in patients with SLE who had high disease activity or renal manifestations at baseline. The safety profile of belimumab was generally consistent with that observed in previous SLE trials. Adverse events were the primary reasons for double‐blind phase withdrawals (belimumab 5.4%, placebo 6.7%). Conclusion: The primary end point of this study was not achieved, but improvement with belimumab versus placebo was observed, suggesting that belimumab remains a suitable treatment option for SLE management in patients of Black African ancestry. [ABSTRACT FROM AUTHOR]

Objective: To investigate long‐term safety and tolerability of anifrolumab, a human monoclonal antibody to the type I interferon (IFN) receptor subunit 1, in patients with moderate‐to‐severe systemic lupus erythematosus (SLE). Methods: This 3‐year, multinational, open‐label extension study included adult patients who completed treatment (48 weeks of anifrolumab or placebo; 12‐week follow‐up) in the MUSE phase IIb randomized controlled trial (RCT). Patients initially received 1,000 mg of anifrolumab intravenously every 4 weeks, which was reduced to 300 mg every 4 weeks based on the benefit/risk profile established in the MUSE trial. Adverse events (AEs) were assessed monthly. Exploratory end points included the SLE Disease Activity Index 2000 (SLEDAI‐2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), pharmacodynamics, and health‐related quality of life (HRQoL). Results: Of the 246 patients who completed the RCT, 218 (88.6%) enrolled in the open‐label extension study, of which 139 (63.8%) completed 3 years of treatment. Approximately 69.7% of patients reported ≥1 AE during the first year of open‐label extension treatment. Frequency and patterns of serious AEs and AEs of special interest over 3 years were consistent with those reported for 1 year of treatment in the RCT. Few patients (6.9%) discontinued treatment due to AEs. No new safety signals were identified. Improvement in the SLEDAI‐2K was sustained over 3 years. SDI and Short Form 36 health survey scores remained stable. Neutralization of type I IFN gene signatures was maintained in the IFN‐high population, and C3, C4, and anti–double‐stranded DNA showed trends toward sustained improvement. Conclusion: Long‐term anifrolumab treatment demonstrates an acceptable safety profile with sustained improvement in SLE disease activity, HRQoL, and serologic measures. [ABSTRACT FROM AUTHOR]

The aims of the present study are to observe the prevalence of hypothyroidism (both subclinical and overt hypothyroidism), its association with dyslipidemia and whether replacement therapy with thyroid hormone has an effect on plasma lipid profile of hypothyroid patients. This prospective study of one-year duration recruited 232 clinically suspected patients belonging to both sexes and age group between 20-70 years attending OPD of endocrinology department of MLN Medical College, Allahabad. Patients were screened for T3, T4 and TSH and those who were euthyroid (52 cases) were excluded from the study. Thus, the present study included only 180 newly diagnosed cases of hypothyroidism. Levothyroxine replacement therapy was administered and patients were assessed every 3-4 months for an effect on lipid profile and body mass index during the study period. In both subclinical and overt hypothyroidism associated with dyslipidemia, replacement therapy with levothyroxine resulted in reversal to normal in significant number of cases. Although majority of hypothyroid cases were overweight yet therapy with levothyroxine caused no significant changes in BMI in all grades of obesity. [ABSTRACT FROM AUTHOR]

Objective. The autopsy and clinical information on children dying with anti-SSA/Ro-associated cardiac manifestations of neonatal lupus (cardiac NL) were examined to identify patterns of disease, gain insight into pathogenesis and enhance the search for biomarkers and preventive therapies.Methods. A retrospective analysis evaluating reports from 18 autopsies of cardiac NL cases and clinical data from the Research Registry for Neonatal Lupus was performed.Results. Of the 18 cases with autopsies, 15 had advanced heart block, including 3 who died in the second trimester, 9 in the third trimester and 3 post-natally. Three others died of cardiomyopathy without advanced block, including two dying pre-natally and one after birth. Pathological findings included fibrosis/calcification of the atrioventricular (AV) node, sinoatrial (SA) node and bundle of His, endocardial fibroelastosis (EFE), papillary muscle fibrosis, valvular disease, calcification of the atrial septum and mononuclear pancarditis. There was no association of pathology with the timing of death except that in the third-trimester deaths more valvular disease and/or extensive conduction system abnormalities were observed. Clinical rhythm did not always correlate with pathology of the conduction system, and the pre-mortem echocardiograms did not consistently detect the extent of pathology.Conclusion. Fibrosis of the AV node/distal conduction system is the most characteristic histopathological finding. Fibrosis of the SA node and bundle of His, EFE and valve damage are also part of the anti-Ro spectrum of injury. Discordance between echocardiograms and pathology findings should prompt the search for more sensitive methods to accurately study the phenotype of antibody damage. [ABSTRACT FROM PUBLISHER]

Objective Neonatal lupus (NL) occurs in fetuses exposed to maternal anti-SSA/Ro and/or anti-SSB/La antibodies, although the mothers themselves may not manifest any clinical disease. A focus on transmission of risk factors for NL from maternal grandparents to mothers of children with NL may yield dividends toward understanding the aggregation of autoantibodies and genetic factors in affected families. This study was perforned to determine the role of maternal grandparents in the development of the autoimmune phenotype of mothers of children with NL. Methods Fifty-one mothers of children with cardiac and/or cutaneous NL, 48 maternal grandmothers, and 35 maternal grandfathers in the Research Registry for Neonatal Lupus were interrogated for clinical symptoms by questionnaire and underwent laboratory assessments, including determination of anti-SSA/Ro and anti-SSB/La antibody status (by enzyme-linked immunosorbent assay) and genotype at rs1800629 ( TNFα) and rs7775397 ( C6orf10) (allelic discrimination). The transmission disequilibrium test (TDT) was computed to test for nonrandom transmission from maternal grandparents to mothers of children with NL. Results The common phenotypic feature in mothers of children with NL was the autoantibody and not the clinical profile; 7 had lupus, 14 had Sjögren's syndrome, 7 had both, and 23 were asymptomatic. Mothers of children with NL were significantly enriched for the risk alleles at both TNFα and C6orf10. The grandparents of children with NL carried minimal burden for autoimmune disease or abnormal antibody production and were not enriched in the genetic risk factors. However, the TDT analysis showed significant excess transmission of the risk alleles at both TNFα (odds ratio [OR] 6.67, P = 3.93 × 10−4) and C6orf10 (OR 35.0, P = 3.74 × 10−5) to mothers of children with NL. Conclusion Mothers of children with NL are enriched for the TNFα and C6orf10 risk alleles, which are preferentially inherited from the asymptomatic maternal grandparents. These findings support the hypothesis that the development of NL and genetic etiology are multigenerational. [ABSTRACT FROM AUTHOR]

The aim of this study was to observe whether levothyroxine replacement therapy has an effect on hypertension in patients of hypothyroidism. This prospective study included all newly diagnosed cases of hypothyroidism (overt or subclinical) with hypertension, of either sex between 21-70 years of age. Levothyroxine replacement therapy was administered continuously during study period. Patients were clinically assessed for blood pressure before and every 3-4 monthly on levothyroxine therapy. Statistical analysis was carried out using a paired Student's t-test. During one year study period, out of 180 newly diagnosed hypothyroid cases enrolled, 88 had overt hypothyroidism (OH) and 92 subclinical hypothyroidism (SH). Male: female ratio was 1: 6.5. Of these, hypertension was present in 51 (28.33%) patients (33 OH and 18 SH). Only diastolic blood pressure was raised in 28(54.9%) cases, systolic in 12 (23.53%) and both systolic and diastolic in 11 (21.57%) cases. Incidence of only diastolic hypertension was comparatively more in overt hypothyroidism (57.57%) than subclinical hypothyroidism (50%). Complete reversal of hypertension was observed in 8 out of 17 SH and 18 out of 29 OH cases while partial reversal was noted in one case in each category. A statistically significant decrease in mean values of both systolic and diastolic blood pressure was observed in patients of SH as well as OH. Hypertension is fairly common in patients of hypothyroidism. Replacement therapy with levothyroxine is quite helpful in reversing hypertension, a potential cardiovascular risk factor. [ABSTRACT FROM AUTHOR]