Search

Context: A variety of topical and systemic drugs are available to treat primary Sjögren syndrome, although no evidence-based therapeutic guidelines are currently available.Objective: To summarize evidence on primary Sjögren syndrome drug therapy from randomized controlled trials.Data Sources: We searched MEDLINE and EMBASE for articles on drug therapy for primary Sjögren syndrome published between January 1, 1986, and April 30, 2010.Study Selection: Controlled trials of topical and systemic drugs including adult patients with primary Sjögren syndrome were selected as the primary information source.Results: The search strategy yielded 37 trials. A placebo-controlled trial found significant improvement in the Schirmer and corneal staining scores, blurred vision, and artificial tear use in patients treated with topical ocular 0.05% cyclosporine. Three placebo-controlled trials found that pilocarpine was associated with improvements in dry mouth (61%-70% vs 24%-31% in the placebo group) and dry eye (42%-53% vs 26%). Two placebo-controlled trials found that cevimeline was associated with improvement in dry mouth (66%-76% vs 35%-37% in the placebo group) and dry eye (39%-72% vs 24%-30%). Small trials (<20 patients) found no significant improvement in sicca outcomes for oral prednisone or hydroxychloroquine and limited benefits for immunosuppressive agents (azathioprine and cyclosporine). A large trial found limited benefits for oral interferon alfa-2a. Two placebo-controlled trials of infliximab and etanercept did not achieve the primary outcome (a composite visual analog scale measuring joint pain, fatigue, and dryness); neither did 2 small trials (<30 patients) testing rituximab, although significant results were observed in some secondary outcomes and improvement compared with baseline.Conclusions: In primary Sjögren syndrome, evidence from controlled trials suggests benefits for pilocarpine and cevimeline for sicca features and topical cyclosporine for moderate or severe dry eye. Anti-tumor necrosis factor agents have not shown clinical efficacy, and larger controlled trials are needed to establish the efficacy of rituximab. [ABSTRACT FROM AUTHOR]

Aim: Currently, several different instruments are used to measure disease activity and extent in clinical trials of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, leading to division among investigative groups and difficulty comparing study results. An exercise comparing six different vasculitis instruments was performed.Methods: A total of 10 experienced vasculitis investigators from 5 countries scored 20 cases in the literature of Wegener granulomatosis or microscopic polyangiitis using 6 disease assessment tools: the Birmingham Vasculitis Activity Score (BVAS), The BVAS for Wegener granulomatosis (BVAS/WG), BVAS 2003, a Physician Global Assessment (PGA), the Disease Extent Index (DEI) and the Five Factor Score (FFS). Five cases were rescored by all raters.Results: Reliability of the measures was extremely high (intraclass correlations for the six measures all = 0.98). Within each instrument, there were no significant differences or outliers among the scores from the 10 investigators. Test/retest reliability was high for each measure: range = 0.77 to 0.95. The scores of the five acute activity measures correlated extremely well with one another.Conclusions: Currently available tools for measuring disease extent and activity in ANCA-associated vasculitis are highly correlated and reliable. These results provide investigators with confidence to compare different clinical trial data and helps form common ground as international research groups develop new, improved and universally accepted vasculitis disease assessment instruments. [ABSTRACT FROM AUTHOR]

PURPOSE: Rehabilitation research information can be obtained from various bibliographic sources. Nevertheless, search strategies and terminologies differ from one database to another making it challenging for the novice user or users of multiple databases. This paper discusses a novel approach of using the International Classification of Functioning, Disability and Health (ICF) codes to retrieve rehabilitation research information. METHOD: A crosswalk was created by mapping the Center for International Rehabilitation Research and Information Exchange's (CIRRIE) subject headings to the two-level ICF codes and a search interface was developed (available at: http://cirrie.buffalo.edu/icf/crosswalk.php) so that users can input ICF codes instead of conventional subject headings. RESULTS: About 62% of all CIRRIE subject headings were mapped to equivalent ICF codes. Among the CIRRIE subject heading that were mapped, 43% were mapped to the Environmental Factors, followed by 34% mapped to the Activities and Participation component of the ICF. CONCLUSION: Although the ICF was not conceived or developed as a system of formal terminology, it can be used effectively for information retrieval in conjunction with an existing vocabulary. This paper describes the first attempt in implementing the use of ICF for information retrieval. [ABSTRACT FROM AUTHOR]

Giant cell arteritis (GCA) is a major cause of vision loss and other health problems. Classic histopathological findings include transmural inflammation with mononuclear cells and multi-nucleated giant cells. Laboratory investigation often demonstrates elevated acute phase reactant levels. GCA symptoms develop abruptly in some patients but more often occur insidiously. Symptoms include headache, scalp tenderness, jaw claudication, and shoulder and hip pain and stiffness. Polymyalgia rheumatica occurs in up to half of patients with GCA. Some patients have aortic involvement. Information from both temporal artery biopsies and MRI studies can assist in making the diagnosis. High-dose corticosteroids and low-dose aspirin are the cornerstones of therapy, but corticosteroids have numerous adverse effects. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To provide a single source for the best available estimates of the US prevalence of and number of individuals affected by arthritis overall, rheumatoid arthritis, juvenile arthritis, the spondylarthritides, systemic lupus erythematosus, systemic sclerosis, and Sjögren's syndrome. A companion article (part II) addresses additional conditions. METHODS: The National Arthritis Data Workgroup reviewed published analyses from available national surveys, such as the National Health and Nutrition Examination Survey and the National Health Interview Survey (NHIS). For analysis of overall arthritis, we used the NHIS. Because data based on national population samples are unavailable for most specific rheumatic conditions, we derived estimates from published studies of smaller, defined populations. For specific conditions, the best available prevalence estimates were applied to the corresponding 2005 US population estimates from the Census Bureau, to estimate the number affected with each condition. RESULTS: More than 21% of US adults (46.4 million persons) were found to have self-reported doctor-diagnosed arthritis. We estimated that rheumatoid arthritis affects 1.3 million adults (down from the estimate of 2.1 million for 1995), juvenile arthritis affects 294,000 children, spondylarthritides affect from 0.6 million to 2.4 million adults, systemic lupus erythematosus affects from 161,000 to 322,000 adults, systemic sclerosis affects 49,000 adults, and primary Sjögren's syndrome affects from 0.4 million to 3.1 million adults. CONCLUSION: Arthritis and other rheumatic conditions continue to be a large and growing public health problem. Estimates for many specific rheumatic conditions rely on a few, small studies of uncertain generalizability to the US population. This report provides the best available prevalence estimates for the US, but for most specific conditions, more studies generalizable to the US or addressing understudied populations are needed. [ABSTRACT FROM AUTHOR]

Background: The utility of antineutrophil cytoplasmic antibody (ANCA) levels to guide the management of patients with Wegener granulomatosis remains controversial.Objective: To determine whether pro-proteinase 3 (PR3)-ANCA levels are a better measure of disease activity than mature-PR3-ANCA levels, whether decreases in either level are associated with shorter time to remission, and whether increases are followed by relapse.Design: Prospective, observational cohort study.Setting: 8 United States medical centers that participated in a treatment trial for Wegener granulomatosis.Patients: 156 patients with Wegener granulomatosis enrolled during periods of active disease.Measurements: PR3-ANCA levels (by capture enzyme-linked immunosorbent assay) and disease activity (by the Birmingham Vasculitis Activity Score for Wegener granulomatosis).Results: The ANCA levels were only weakly associated with disease activity across patients. The longitudinal association within patients was stronger, but changes in ANCA levels explained less than 10% of the variation in disease activity. Decreases in mature- and pro-PR3-ANCA levels were not statistically significantly associated with shorter time to remission, and increases in mature-PR3-ANCA levels (adjusted hazard ratio, 0.8 [95% CI, 0.4 to 1.9]; P = 0.67) and pro-PR3-ANCA levels (adjusted hazard ratio, 1.0 [CI, 0.5 to 2.1]; P = 0.99) were not associated with relapse. The proportion of patients who had relapse within 1 year of an increase in PR3-ANCA levels was 40% for mature-PR3 (CI, 18% to 56%) and 43% for pro-PR3 (CI, 22% to 58%).Limitations: Samples were collected approximately every 3 months. Sensitivity and specificity of ANCA levels for detecting remission and relapse could not be calculated because each patient had different follow-up times.Conclusion: Pro-PR3-ANCA is no better than mature-PR3-ANCA as a measure of Wegener granulomatosis activity. Decreases in PR3-ANCA levels are not associated with shorter time to remission, and increases are not associated with relapse. These findings suggest that ANCA levels cannot be used to guide immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Microscopic polyangiitis (MPA) may present with a syndrome that resembles idiopathic pulmonary fibrosis (IPF). We describe an MPA patient with the clinical presentation of a 'pulmonary-muscle' syndrome in which interstitial lung disease antedated the onset of myopathy. Identification of vasculitis on muscle biopsy was instrumental in recognizing clinical, radiographic, and histopathologic features that were more characteristic of MPA than of IPF. Institution of glucocorticoid and cyclophosphamide therapy led to the induction of a complete remission. The histologic findings in this case implicate subclinical episodes of alveolar hemorrhage as the mechanism of interstitial lung disease in MPA. [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis factor-alpha is present in arteries in giant cell arteritis.Objective: To evaluate the efficacy of infliximab, an anti-tumor necrosis factor-alpha agent, in giant cell arteritis.Design: Randomized, controlled trial.Setting: 22 sites in the United States, the United Kingdom, Belgium, Italy, and Spain.Patients: 44 patients with newly diagnosed giant cell arteritis that was in glucocorticosteroid-induced remission.Intervention: Participants were randomly assigned in a 2:1 ratio to receive infliximab (5 mg/kg of body weight) or placebo. Sixteen patients were assigned to glucocorticosteroid plus placebo, and 28 patients to glucocorticosteroid plus infliximab.Measurements: End points were measured through week 22, when an interim analysis resulted in early stopping of the planned 54-week trial. Primary end points were the number of patients who remained free of relapse through week 22 and adverse events. Secondary end points were time to first relapse, biomarkers, cumulative glucocorticosteroid dose, and the number of patients who remained relapse-free while the glucocorticosteroid dosage was tapered to 10 mg/d.Results: Infliximab therapy did not increase the proportion of patients without relapse at week 22 compared with placebo (43% vs. 50%, respectively; difference, -7 percentage points [95% CI, -38 to 23 percentage points; P = 0.65), nor did it increase the proportion of patients whose glucocorticosteroid dosages were tapered to 10 mg/d without relapse (61% vs. 75%, respectively; difference, -14 percentage points [CI, -42 to 14 percentage points]; P = 0.31). The incidence of infection was 71% with infliximab and 56% with placebo (difference, 15 percentage points [CI, -14 to 45 percentage points]).Limitations: The sample was too small to rule out modest effects of infliximab and included only patients with a new diagnosis. Only one dose of infliximab was evaluated, and the study was terminated early.Conclusions: This trial is too small to draw definitive conclusions, but it provides evidence that using infliximab as maintenance therapy in patients in glucocorticoid-induced remission of newly diagnosed giant cell arteritis is of no benefit and may be harmful. If infliximab has benefit, it is unlikely to be great. ClinicalTrials.gov registration number: NCT00076726. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Etanercept is a soluble fusion protein designed to inhibit tumor necrosis factor (TNF). During the Wegener's Granulomatosis Etanercept Trial (WGET), a placebo-controlled trial of etanercept given in addition to standard therapy for remission induction and maintenance, more solid malignancies were observed in the etanercept group than in the group treated with standard therapy alone. This study was undertaken to further explore the potential association between anti-TNF therapy and the development of malignancy in these patients. METHODS: One hundred eighty patients with active WG were enrolled and followed up for a median of 27 months. At enrollment, disease characteristics, treatment history, specific medical history items, and information about previous WG treatments and risk factors for malignancy were recorded. During the trial, the occurrence of malignancies and other adverse events was recorded prospectively. RESULTS: All 6 solid malignancies observed during the WGET occurred in the etanercept group (P = 0.01 versus placebo group); based on a comparison of age- and sex-specific incidence rates, 1.92 solid malignancies would have been expected in this group. The solid malignancies included 2 cases of mucinous adenocarcinoma of the colon, 1 each of metastatic cholangiocarcinoma, renal cell carcinoma, and breast carcinoma, and 1 recurrent liposarcoma. There were no differences between the 2 treatment groups in sex distribution, disease severity, personal or family history of cancer, or tobacco and alcohol use. The etanercept group was older at baseline and less likely to be newly diagnosed with WG at the time of randomization. Patients who developed solid tumors were older than patients who did not. All etanercept-treated patients who developed solid tumors were also treated with cyclophosphamide during the trial. However, there were no differences between the groups in the amount of cyclophosphamide received during the trial or the percentage who had received cyclophosphamide before enrollment. There were also no differences in the mean duration of daily cyclophosphamide therapy or the maximum daily cyclophosphamide dosage before enrollment. CONCLUSION: Data from the WGET, the first substantial reported experience of the combined use of etanercept and cyclophosphamide in the treatment of WG, indicate that the combination of TNF inhibition and cyclophosphamide may heighten the risk of cancer beyond that observed with cyclophosphamide alone. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To analyze damage occurring in patients with Wegener's granulomatosis (WG) enrolled in the WG Etanercept Trial (WGET) and to correlate that damage with disease activity, adverse events, and quality of life. METHODS: The Vasculitis Damage Index (VDI) was applied to all 180 patients at trial entry and every 6 months throughout the trial. Items of damage were analyzed by presumed etiology (i.e., secondary to WG, to therapy, or both) and time of occurrence. Spearman's rank correlation coefficients were calculated between VDI scores and the Birmingham Vasculitis Activity Score for WG (BVAS/WG), frequency of flares, number of adverse events, and the patients' quality-of-life assessments. RESULTS: The mean VDI score was 1.3 at the study enrollment and 1.8 at the end of the trial. This increase was due to damage that occurred despite (or because of) therapy, including visual impairment, hearing loss, nasal blockade, pulmonary fibrosis, hypertension, renal insufficiency, peripheral neuropathy, gonadal failure, and diabetes mellitus. Only 11% of the enrolled patients had not sustained a single VDI item after 1 year of enrollment. When adjusted for baseline VDI, the baseline BVAS/WG correlated moderately well with the VDI score at 1 year (r = 0.20, P = 0.015). Increases in adjusted VDI scores also correlated with the number of adverse events, particularly among patients with limited WG (P = 0.06). CONCLUSION: Damage from both active disease and its treatment remain important problems for patients with WG. Despite the dramatic improvements in patient survival achieved over the last several decades, only a few patients with WG emerge from a period of active disease without sustaining some damage from the disease itself, its treatment, or both. An important measure of future therapeutic approaches will be their ability to reduce the damage accrued over time. [ABSTRACT FROM AUTHOR]

Congestive heart failure (CHF) is a common and increasing problem among older persons. Symptoms associated with CHF include edema, fatigue, dyspnea, limited exercise tolerance, and significant activity limitation. Using a comprehensive review of literature, this article describes the public health burden arising out of CHF in the United States. It describes CHF in terms of functional limitation and disability in the elderly following the National Center for Medical Rehabilitation and Research (NCMRR) disability model. The use of home based interventions (HBI) to assist people with CHF is discussed. [ABSTRACT FROM AUTHOR]

Background: Toxicities associated with oral corticosteroids (OCS) are well described. Targeted biologics for severe asthma (SA) substantially reduce OCS exposure with the potential to reduce cumulative OCS-related toxicities. The Glucocorticoid Toxicity Index (GTI) systematically assesses OCS-related toxicity; the GTI Aggregate Improvement Score (AIS) is a bidirectional measure of total toxicity change with a minimal clinically important difference (MCID) of ≤-10., Objective: This study was a longitudinal assessment of patients with SA treated with biologic therapies to assess the trajectory of OCS-related toxicity and predictors of toxicity improvement., Methods: A total of 89 patients with SA had GTI assessments at baseline and after 1 and 3 years of biologic therapy., Results: At 3 years, daily prednisolone use continued to decrease (6.9 mg/day [4.0, 9.4] year 1 vs 0.8 mg/day [0.0, 3.7] year 3, P < .001), OCS-related toxicity continued to decline (AIS at 3 years -36 [-94, 19]), and 61% (54 of 89) met the AIS MCID. There was a significant positive correlation between toxicity outcomes at years 1 and 3 (ρ 0.65, P < .001). Nearly half (49%) met the AIS MCID at both years 1 and 3, but 29% of the cohort did not meet the AIS MCID at either time point. Toxicity change at year 1 was predictive of toxicity change at year 3 for 79%. Toxicity reduction was not proportional to OCS reduction; there were no prebiologic characteristics that predicted toxicity reduction., Conclusions: After 3 years of biologic treatment, 61% of patients with SA had clinically significant toxicity improvement. Individual toxicity outcomes at year 1 are associated with longitudinal outcomes, suggesting that for some, additional interventions are needed alongside OCS reduction to decrease morbidity., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) face excess mortality compared with the general population. Mortality in clinical epidemiology research is often examined using death certificate diagnosis codes; however, the sensitivity of such codes in AAV is unknown., Methods: We performed a retrospective cohort study using the Mass General Brigham AAV Cohort, including patients with AAV who died between 2002 and 2019. Causes of death were determined by electronic health record (EHR) review (reference gold standard) and via cause of death diagnosis codes on death certificates. We calculated the sensitivity of death certificate diagnosis codes for AAV., Results: Of 684 patients in the registry, 184 died, 92 (52 %) of whom had adequate EHR data available determine cause of death and 72 (40 %) of whom had both EHR and death certificate data available. Death due to AAV, infection, cardiovascular disease, and cancer occurred in 8 %, 29 %, 5 %, and 18 %, respectively, when ascertained by manual review, as opposed to 0 %, 11 %, 25 %, and 21 %, as determined by death certificates. The sensitivity of AAV diagnosis codes for AAV was 16.6 % (95 % CI: 10.5, 22.6) among all patients with death certificate data available., Conclusion: In a contemporary cohort of patients with AAV, infection was the most common cause of death, while death due to AAV itself was rare. We found a high degree of discordance between causes of death determined by manual review and death certificate diagnosis codes. Mortality research on AAV should include linkage to medical records data to reduce potential bias., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Guy Katz reports financial support was provided by Rheumatology Research Foundation. Zachary S. Wallace reports financial support was provided by National Institutes of Health. Guy Katz reports financial support was provided by National Institutes of Health. Guy Katz reports a relationship with Sanofi that includes: funding grants. Guy Katz reports a relationship with GLG Consulting that includes: consulting or advisory. Guy Katz reports a relationship with Evolve Medical Education that includes: speaking and lecture fees. Guy Katz reports a relationship with NEJM Resident 360 that includes: speaking and lecture fees. Guy Katz reports a relationship with IgG4ward that includes: speaking and lecture fees. Guy Katz reports a relationship with Amgen Inc that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Amgen Inc that includes: consulting or advisory and funding grants. Zachary S. Wallace reports a relationship with Bristol Myers Squibb Co that includes: funding grants. Zachary S. Wallace reports a relationship with Sanofi that includes: consulting or advisory and funding grants. Zachary S. Wallace reports a relationship with Viela Bio that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Adicet Bio Inc that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Horizon Therapeutics USA Inc that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Zenas BioPharma that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Pharmaceutical Product Development that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Medpace Inc that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Novartis that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Shinogi that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Visterra Inc that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Patients with autoimmune blistering diseases (AIBDs) are often exposed to chronic glucocorticoid (GC) treatment with many side effects. Glucocorticoid-induced myopathy (GIM) is a well-established side effect, which particularly affects the proximal muscles. The Glucocorticoid Toxicity Index (GTI) is a validated global assessment tool which quantifies GC toxicity over time., Objectives: This study marks the first study which analyses GIM in patients with AIBDs. The objectives of this study were to utilize the GTI to investigate the nature and prevalence of GIM in AIBD patients and explore potential risk factors., Methods: This international cohort study was conducted in blistering disease clinics across Australia, China, Greece, Iran, Japan, the Philippines, Turkey and the United States of America between February 2019 and July 2023. The GTI tool was completed by a medical practitioner at each patient visit. Data related to glucocorticoid toxicity were entered into the Steritas GTI 2.0 to generate an aggregate improvement and cumulative worsening score at each visit., Results: The study included 139 patients. There were 132 episodes of myopathy, and 47.5% of patients developed muscle weakness at some point during the study period. Cumulative GC dose correlated positively with myopathy risk, while average dose and treatment duration were not significant. Older age, male gender and obesity more than doubled the likelihood of developing GIM., Conclusions: GIM is a common side effect experienced by AIBD patients on GC treatment. Muscle weakness is less likely to occur if cumulative GC dose is less than 0.75 mg/kg/day. Studies of exercise programs to mitigate myopathy and newer alternative treatments to reduce cumulative GC dose should be considered., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Objectives: Hypocomplementaemia is common in patients with IgG4-related disease (IgG4-RD). We aimed to determine the IgG4-RD features associated with hypocomplementaemia and investigate mechanisms of complement activation in this disease., Methods: We performed a single-centre cross-sectional study of 279 patients who fulfilled the IgG4-RD classification criteria, using unadjusted and multivariable-adjusted logistic regression to identify factors associated with hypocomplementaemia., Results: Hypocomplementaemia was observed in 90 (32%) patients. In the unadjusted model, the number of organs involved (OR 1.42, 95% CI 1.23 to 1.63) and involvement of the lymph nodes (OR 3.87, 95% CI 2.19 to 6.86), lungs (OR 3.81, 95% CI 2.10 to 6.89), pancreas (OR 1.66, 95% CI 1.001 to 2.76), liver (OR 2.73, 95% CI 1.17 to 6.36) and kidneys (OR 2.48, 95% CI 1.47 to 4.18) were each associated with hypocomplementaemia. After adjusting for age, sex and number of organs involved, only lymph node (OR 2.59, 95% CI 1.36 to 4.91) and lung (OR 2.56, 95% CI 1.35 to 4.89) involvement remained associated with hypocomplementaemia while the association with renal involvement was attenuated (OR 1.6, 95% CI 0.92 to 2.98). Fibrotic disease manifestations (OR 0.43, 95% CI 0.21 to 0.87) and lacrimal gland involvement (OR 0.53, 95% CI 0.28 to 0.999) were inversely associated with hypocomplementaemia in the adjusted analysis. Hypocomplementaemia was associated with higher concentrations of all IgG subclasses and IgE (all p<0.05). After adjusting for serum IgG1 and IgG3, only IgG1 but not IgG4 remained strongly associated with hypocomplementaemia., Conclusions: Hypocomplementaemia in IgG4-RD is not unique to patients with renal involvement and may reflect the extent of disease. IgG1 independently correlates with hypocomplementaemia in IgG4-RD, but IgG4 does not. Complement activation is likely involved in IgG4-RD pathophysiology., Competing Interests: Competing interests: The authors declare competing interests with the Rheumatology Research Foundation, NIH, Sanofi, Zenas, Amgen, Genentech, Sana, National Multiple Sclerosis Society, GlaxoSmithKline, Helmsley Charitable Trust, AstraZeneca, Bristol Myers Squibb, Novartis, Alexion Pharmaceuticals, ANI Pharmaceuticals, Aurinia Pharmaceuticals, Exagen Diagnostics, Kypha, Pfizer, UpToDate, The Rheumatology Education Group, Lupus Foundation of America-Heartland Chapter, St Louis Rheumatology Chapter, Lupus Research Alliance, National Scleroderma Foundation, AbbVie, Acepodia, Alpine Immune Sciences, Argenx, Connect Biopharma, CTI BioPharma, Horizon Therapeutics, iCell Gene Therapeutics, IQVIA, Prometheus Biosciences/Merck, Q32 Bio, Salvina Therapeutics, IgG4ward! Foundation, Achillion Pharmaceuticals, Annexon Pharmaceuticals, Arrowhead Pharmaceuticals, Autobahn Therapeutics, Avidity Partners, BioMarin Pharmaceuticals, Broadwing Bio, Celldex Therapeutics, 4D Molecular Therapeutics, HiBIO, Janssen, Kypha, Merck KGaA, Takeda Pharmaceuticals, Compliment Corporation, Gemini Therapeutics, Leducq Foundation, Be Bio Pharma, Paratus, Octagon Therapeutics, Ab Pro, Viela Bio, MedPace and BioCryst., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Background: IgG4-related disease is a multiorgan, relapsing, fibroinflammatory, immune-mediated disorder with no approved therapy. Inebilizumab targets and depletes CD19+ B cells and may be effective for treating patients with IgG4-related disease., Methods: In this phase 3, multicenter, double-blind, randomized, placebo-controlled trial, adults with active IgG4-related disease underwent randomization in a 1:1 ratio to receive inebilizumab (300-mg intravenous infusions on days 1 and 15 and week 26) or placebo for a 52-week treatment period. Participants in both groups received identical glucocorticoid tapers. Glucocorticoids were allowed to treat disease flares, but background immunosuppressants were not permitted. The primary end point was the first treated, adjudicated disease flare during the treatment period, assessed in a time-to-event analysis. Key secondary end points were the annualized flare rate and treatment-free and glucocorticoid-free complete remission., Results: A total of 135 participants with IgG4-related disease underwent randomization: 68 participants were assigned to receive inebilizumab and 67 were assigned to receive placebo. Treatment with inebilizumab reduced flare risk; 7 participants (10%) in the inebilizumab group had at least one flare, as compared with 40 participants (60%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.06 to 0.28; P<0.001). The annualized flare rate was lower with inebilizumab than with placebo (rate ratio, 0.14; 95% CI, 0.06 to 0.31; P<0.001). More participants in the inebilizumab group than in the placebo group had flare-free, treatment-free complete remission (odds ratio, 4.68; 95% CI, 2.21 to 9.91; P<0.001) and flare-free, glucocorticoid-free complete remission (odds ratio, 4.96; 95% CI, 2.34 to 10.52; P<0.001). Serious adverse events occurred during the treatment period in 12 of the participants (18%) who received inebilizumab and 6 of the participants (9%) who received placebo., Conclusions: Inebilizumab reduced the risk of flares of IgG4-related disease and increased the likelihood of flare-free complete remission at 1 year, confirming the role of CD19-targeted B-cell depletion as a potential treatment for IgG4-related disease. (Funded by Amgen; MITIGATE ClinicalTrials.gov number, NCT04540497.)., (Copyright © 2024 Massachusetts Medical Society.)

Abstract: Research on IgG4-related disease (IgG4-RD), an autoimmune condition recognized to be a unique disease entity only two decades ago, has processed from describing patients' symptoms and signs to summarizing its critical pathological features, and further to investigating key pathogenic mechanisms. Challenges in gaining a better understanding of the disease, however, stem from its relative rarity-potentially attributed to underrecognition - and the absence of ideal experimental animal models. Recently, with the development of various high-throughput techniques, "omics" studies at different levels (particularly the single-cell omics) have shown promise in providing detailed molecular features of IgG4-RD. While, the application of omics approaches in IgG4-RD is still at an early stage. In this paper, we review the current progress of omics research in IgG4-RD and discuss the value of machine learning methods in analyzing the data with high dimensionality., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Objectives: The pediatric Glucocorticoid Toxicity Index (pGTI) is a new, pediatric-specific tool to quantify glucocorticoid (GC)-related morbidity in children. We evaluated the feasibility and construct validity of retrospective pGTI scoring in patients with pediatric-onset systemic lupus erythematosus (pSLE) and identified risk factors for cumulative toxicity., Methods: We conducted a retrospective cohort study of patients with pSLE treated with GCs at two pediatric centers (1999-2023). GC exposure was estimated using interval-averaged oral prednisone-equivalent dose and cumulative prednisone-equivalent dose. We scored change in GC toxicity every 6 months (±2) using a modified pGTI including 7 of 10 domains. We calculated the Cumulative Worsening Score (CWS), a continuous summation of toxicity accrued. Mixed effects linear regression was used to identify factors associated with CWS., Results: There were 126 patients with pSLE, including 88 with nephritis, with a median of 6 visits/patient. Nearly half (47 %) experienced toxicity in the Blood Pressure domain. Other common toxicities were mood disturbance (25 %), followed by increased body mass index (BMI), striae, and sleep disturbance (21 % each). Decreased growth velocity was observed in 18 %. There was modest correlation between cumulative GC dose and CWS (rho 0.3; p < 0.01). Greater cumulative toxicity was associated with younger age, elevated BMI, and rituximab use at the time of GC initiation, albeit indications for the latter were not captured., Conclusions: Patients with pSLE experience a high burden of GC toxicity, particularly related to blood pressure, BMI, sleep, and growth. Standardized, pediatric-specific GC toxicity assessment is feasible in real-world settings and can facilitate evaluation of strategies to reduce morbidity in children requiring chronic GC treatment., Competing Interests: Declaration of competing interest J.C.C previously received grant funding from GSK for investigator-driven research outside the scope of this work. Professor Stone's hospital, the Massachusetts General Hospital, owns the intellectual property of the pGTI. The worldwide licensing rights to the pGTI are controlled by Steritas, LLC. Professor Stone co-founded Steritas and is the chair of the Scientific Advisory Board but has no fiduciary responsibility at the company. The remaining co-authors have no other relevant financial conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)