Showing papers by "Christine A. Peschken published in 2019"

Antinuclear Antibody-Negative Systemic Lupus Erythematosus in an International Inception Cohort.

Abstract: Objective The spectrum of antinuclear antibodies (ANAs) is changing to include both nuclear staining as well as cytoplasmic and mitotic cell patterns (CMPs) and accordingly a change is occurring in terminology to anticellular antibodies. This study examined the prevalence of indirect immunofluorescence (IIF) anticellular antibody staining using the Systemic Lupus International Collaborating Clinics inception cohort. Methods Anticellular antibodies were detected by IIF on HEp-2000 substrate using the baseline serum. Three serologic subsets were examined: ANA positive (presence of either nuclear or mixed nuclear/CMP staining), anticellular antibody negative (absence of any intracellular staining), and isolated CMP staining. The odds of being anticellular antibody negative versus ANA or isolated CMP positive was assessed by multivariable analysis. Results A total of 1,137 patients were included; 1,049 (92.3%) were ANA positive, 71 (6.2%) were anticellular antibody negative, and 17 (1.5%) had an isolated CMP. The isolated CMP-positive group did not differ from the ANA-positive or anticellular antibody-negative groups in clinical, demographic, or serologic features. Patients who were older (odds ratio [OR] 1.02 [95% confidence interval (95% CI) 1.00, 1.04]), of white race/ethnicity (OR 3.53 [95% CI 1.77, 7.03]), or receiving high-dose glucocorticoids at or prior to enrollment (OR 2.39 [95% CI 1.39, 4.12]) were more likely to be anticellular antibody negative. Patients on immunosuppressants (OR 0.35 [95% CI 0.19, 0.64]) or with anti-SSA/Ro 60 (OR 0.41 [95% CI 0.23, 0.74]) or anti-U1 RNP (OR 0.43 [95% CI 0.20, 0.93]) were less likely to be anticellular antibody negative. Conclusion In newly diagnosed systemic lupus erythematosus, 6.2% of patients were anticellular antibody negative, and 1.5% had an isolated CMP. The prevalence of anticellular antibody-negative systemic lupus erythematosus will likely decrease as emerging nomenclature guidelines recommend that non-nuclear patterns should also be reported as a positive ANA.

Comorbid anxiety, depression, and cognition in MS and other immune-mediated disorders

Abstract: Objective To determine whether anxiety and depression are associated with cognition in multiple sclerosis (MS), and whether these associations are similar in other immune-mediated inflammatory diseases (IMID; including inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]) and in anxious/depressed individuals (ANX/DEP) without an IMID. Methods Participants (MS: n = 255; IBD: n = 247; RA: n = 154; ANX/DEP: n = 308) completed a structured psychiatric interview, the Hospital Anxiety and Depression Scale, and cognitive testing, including the Symbol Digit Modalities Test, the California Verbal Learning Test, and Letter Number Sequencing test. Test scores were converted to age-, sex-, and education-adjusted z scores. We evaluated associations of anxiety and depression with the cognitive z scores using multivariate linear models, adjusting for disease cohort. Results All cohorts exhibited higher rates of impairment (i.e., z less than or equal to −1.5) in the domains of processing speed, verbal learning, and delayed recall memory relative to general population norms. Higher levels of anxiety symptoms were associated with slower processing speed, lower verbal learning, and lower working memory performance (all p Conclusion Anxiety and depression are associated with lower cognitive function in MS, with a similar pattern observed in persons with other IMID, including IBD and RA, and persons without an IMID. Managing symptoms of anxiety and of depression in MS, as well as other IMIDs, is important to mitigate their effect on cognition.

Psychosis in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study.

Abstract: Objective: To determine, in a large, multiethnic/multiracial, prospective inception cohort of patients with systemic lupus erythematosus (SLE), the frequency, attribution, clinical, and autoantibody associations with lupus psychosis and the short- and long-term outcomes as assessed by physicians and patients. Methods: Patients were evaluated annually for 19 neuropsychiatric (NP) events including psychosis. Scores on the Systemic Lupus Erythematosus Disease Activity Index 2000, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and the Short Form 36 (SF-36) were recorded. Time to event and linear regressions were used as appropriate. Results: Of 1,826 SLE patients, 88.8% were female and 48.8% were Caucasian. The mean ± SD age was 35.1 ± 13.3 years, the mean ± SD disease duration was 5.6 ± 4.2 months, and the mean ± SD follow-up period was 7.4 ± 4.5 years. There were 31 psychotic events in 28 of 1,826 patients (1.53%), and most patients had a single event (26 of 28 [93%]). In the majority of patients (20 of 25 [80%]) and events (28 of 31 [90%]), psychosis was attributed to SLE, usually either in the year prior to or within 3 years of SLE diagnosis. Positive associations (hazard ratios [HRs] and 95% confidence intervals [95% CIs]) with lupus psychosis were previous SLE NP events (HR 3.59 [95% CI 1.16–11.14]), male sex (HR 3.0 [95% CI 1.20–7.50]), younger age at SLE diagnosis (per 10 years) (HR 1.45 [95% CI 1.01–2.07]), and African ancestry (HR 4.59 [95% CI 1.79–11.76]). By physician assessment, most psychotic events resolved by the second annual visit following onset, in parallel with an improvement in patient-reported SF-36 summary and subscale scores. Conclusion: Psychosis is an infrequent manifestation of NPSLE. Generally, it occurs early after SLE onset and has a significant negative impact on health status. As determined by patient and physician report, the short- and long-term outlooks are good for most patients, although careful follow-up is required.

Evaluating the Properties of a Frailty Index and Its Association With Mortality Risk Among Patients With Systemic Lupus Erythematosus.

Abstract: Objective: To evaluate the properties of a frailty index (FI), constructed using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort, as a novel health measure in systemic lupus erythematosus (SLE). Methods: For this secondary analysis, the baseline visit was defined as the first study visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short-Form 36 [SF-36] scores) were assessed. The SLICC-FI was constructed using baseline data. The SLICC-FI comprises 48 health deficits, including items related to organ damage, disease activity, comorbidities, and functional status. Content, construct, and criterion validity of the SLICC-FI were assessed. Multivariable Cox regression was used to estimate the association between baseline SLICC-FI values and mortality risk, adjusting for demographic and clinical factors. Results: In the baseline data set of 1,683 patients with SLE, 89% were female, the mean ± SD age was 35.7 ± 13.4 years, and the mean ± SD disease duration was 18.8 ± 15.7 months. At baseline, the mean ± SD SLICC-FI score was 0.17 ± 0.08 (range 0–0.51). Baseline SLICC-FI values exhibited the expected measurement properties and were weakly correlated with baseline SDI scores (r = 0.26, P < 0.0001). Higher baseline SLICC-FI values (per 0.05 increment) were associated with increased mortality risk (hazard ratio 1.59, 95% confidence interval 1.35–1.87), after adjusting for age, sex, steroid use, ethnicity/region, and baseline SDI scores. Conclusion: The SLICC-FI demonstrates internal validity as a health measure in SLE and might be used to predict future mortality risk. The SLICC-FI is potentially valuable for quantifying vulnerability among patients with SLE, and adds to existing prognostic scores.

Osteopontin and disease activity in patients with recent-onset systemic Lupus Erythematosus: Results from the SLICC Inception Cohort

Abstract: Objective. In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes. Methods. We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively. Results. Compared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01). Conclusion. The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.

Low aspirin use and high prevalence of pre-eclampsia risk factors among pregnant women in a multinational SLE inception cohort

Abstract: Women with systemic lupus erythematosus (SLE) carry a substantially higher risk for pre-eclampsia compared with the general population.1 Aspirin reduces the risk of pre-eclampsia in high-risk pregnancies by more than half2 and thus is recommended in SLE.3–5 The European League Against Rheumatism recommends aspirin in SLE pregnancies, particularly in those with nephritis or positive antiphospholipid antibodies (aPL).5 Despite this, little is known about current practice. Therefore, we assessed the prevalence of aspirin use in SLE pregnancies within the Systemic Lupus International Collaborating Clinics inception cohort, which has been described elsewhere.6 SLE women aged 18–45 with a pregnancy documented at one or more annual study visits (spanning 2000–2017) were included. For each pregnant visit, aspirin use, traditional pre-eclampsia risk factors (hypertension, chronic kidney disease, diabetes, nulliparity, body mass index ≥35, age >40), aPL and active lupus nephritis were assessed (see variable definitions in online supplementary material). Aspirin use was compared among those with and without each/any risk factor, and over time. We identified 475 pregnancies among 300 women. Mean SLE duration at the time of pregnancy was 5.6 years (SD 3.1). Half (51%) of pregnancies had ≥1 traditional pre-eclampsia risk factor, 34/104 (33%) had positive aPL and 53/475 (11%) had …

Persistent Disease Activity Remains a Burden for Patients with Systemic Lupus Erythematosus

Abstract: Objective. Persistent systemic lupus erythematosus (SLE) disease activity is associated with increased morbidity and mortality. In a multicenter cohort of patients with prevalent SLE, we described persistence, patterns, and predictors of change in disease activity over time. Methods. Based on SLE Disease Activity Index (SLEDAI)-2K scores at cohort entry, patients were classified into 4 groups: low (score 10; VHIGH). Multivariable linear and longitudinal mixed linear regression models were used to identify predictors of change over time in SLEDAI-2K. Results. There were 2019 participants, with declining followup data over 5 years (1326, 580, 274, 186, and 148 patients, respectively). At cohort entry, mean (± SD) age was 42 (± 17) years, disease duration 11 (± 10) years, and 90% were female. The 4 groups included 44% LOW (n = 891), 20% MOD (n = 400), 22% MHIGH (n = 442), and 14% VHIGH (n = 286); therefore, 36% had clinically important SLE activity. The proportion of patients in the LOW group at entry who moved to a higher activity level varied from 30% (167/557) at 1 year, to 49% (41/83) at 3 years, and 54% (30/56) at 5 years. Among 181 patients with MOD to VHIGH entry activity and 3 years of followup, 116 (64.1%) remained active. In all analyses, only higher SLEDAI-2K at cohort entry remained a significant predictor of higher SLEDAI-2K in subsequent years. Conclusion. Higher SLEDAI-2K at study entry was the single major independent predictor of higher SLEDAI-2K over time, reflecting frequent persistence of active disease, even in patients with longstanding disease. This highlights gaps in the optimal treatment of SLE.

A comparison between childhood and adult onset systemic lupus erythematosus adjusted for ethnicity from the 1000 Canadian Faces of Lupus Cohort.

Abstract: Objective Childhood-onset SLE (cSLE) manifests differently than adult-onset SLE (aSLE). This study determined whether ethnic differences contribute to the differences in clinical presentation between the two groups. Methods This cross-sectional study used data from a multi-centred registry from eight adult and four paediatric Canadian centres gathered at study entry. We compared the frequency of clinical manifestations and autoantibodies between aSLE and cSLE. For those with a significant difference, a multivariable logistic regression was performed, adjusting for ethnicity, SLE onset (cSLE vs aSLE), disease duration and centre. Disease activity and damage between aSLE and cSLE were compared after stratifying by disease duration. Results Of 552 aSLE subjects, 502 (90.9%) were female and 381 (69.0%) were Caucasian. Mean age at diagnosis was 37.0 ± 13.6 years and disease duration 10.9 ± 9.6 years. Of 276 cSLE subjects, 231 (83.7%) were female and 101 (36.6%) were Caucasian. Mean age at diagnosis was 12.7 ± 3.3 years and disease duration 5.6 ± 8.2 years. In multivariable regression analysis, aSLE was associated with decreased odds of having a neurologic disorder (odds ratio = 0.49) and increased odds of having aCL antibodies (odds ratio = 1.85). Disease activity and damage accrual scores were higher in aSLE than cSLE within the same disease duration strata, although the differences were not clinically significant. Ethnicity was not associated with any differences in clinical manifestations or autoantibody frequency between aSLE and cSLE. Conclusions Although a crude comparison of aSLE and cSLE yielded several differences in clinical symptoms and autoantibodies, this difference was not attributable to ethnic differences between aSLE and cSLE.

Use of combined hormonal contraceptives among women with systemic lupus erythematosus with and without medical contraindications to oestrogen

Abstract: Objectives. To assess the prevalence of combined hormonal contraceptives (CHCs) in reproductive-age women with SLE with and without possible contraindications and to determine factors associated with their use in the presence of possible contraindications. Methods. This observational cohort study included premenopausal women ages 18-45 years enrolled in the SLICC Registry ≤15 months after SLE onset, with annual assessments spanning 2000-2017. World Health Organization Category 3 or 4 contraindications to CHCs (e.g. hypertension, aPL) were assessed at each study visit. High disease activity (SLEDAI score >12 or use of >0.5 mg/kg/day of prednisone) was considered a relative contraindication. Results. A total of 927 SLE women contributed 6315 visits, of which 3811 (60%) occurred in the presence of one or more possible contraindication to CHCs. Women used CHCs during 512 (8%) visits, of which 281 (55%) took place in the setting of one or more possible contraindication. The most frequently observed contraindications were aPL (52%), hypertension (34%) and migraine with aura (22%). Women with one or more contraindication were slightly less likely to be taking CHCs [7% of visits (95% CI 7, 8)] than women with no contraindications [9% (95% CI 8, 10)]. Conclusion. CHC use was low compared with general population estimates (>35%) and more than half of CHC users had at least one possible contraindication. Many yet unmeasured factors, including patient preferences, may have contributed to these observations. Further work should also aim to clarify outcomes associated with this exposure.

Op0128 systemic lupus erythematosus disease characteristics associated with the type i interferon gene signature: baseline data of the sle prospective observational cohort study (spocs)

Abstract: Background Despite accumulating data on the role of type I interferons (IFN) in the pathogenesis of SLE, real-world, longitudinal clinical data on the type I IFN gene signature (IFNGS) collected from patients with SLE are limited. Objectives This initial analysis of the SLE Prospective Observational Cohort Study (SPOCS; NCT03189875) examined the prevalence of the type I IFNGS (high vs low) and its association with baseline SLE disease characteristics in patients with moderately to severely active SLE receiving standard-of-care treatment. Methods SPOCS is an international, multicenter, prospective observational cohort study of patients enrolled with moderately to severely active SLE (SLEDAI-2K ≥6 at entry) from Australia, Canada, France, Germany, Italy, Spain, the United Kingdom, and the United States; a completion date of 2022 is planned. Patients are evaluated biannually during a 3-year follow-up period. At each visit, data are collected on disease activity and damage, treatment received, type I IFNGS (stratified high or low IFNGS based on a predefined cutoff), and several patient-reported outcomes. Results As of November 15, 2018, a total of 307 patients were enrolled in SPOCS (North America, n=184; Europe, n=123), of whom 96.1% (n=295) were female, with a median age of 46 years (range: 18–88). At study entry, the prevalence of high type I IFNGS was 70.5% (n=210) vs 27.9% (n=83) for low type I IFNGS, with 1.7% (n=5) unknown (table, 9 missing data). IFNGS-high patients were younger than IFNGS-low patients (median: 42.5 years [range: 18–82] vs 50 [19–88], P Conclusion The profile of patients with a baseline high type I IFNGS differed from those with a low type I IFNGS, in that those with a high type I IFNGS comprised a group that were on average younger, had greater SLEDAI-2K scores, were more serologically active, and seemed to have fewer comorbidities. As the lupus community evolves from using a classical clinical classification of patients to one based on molecular signatures, it is important to understand the role of the type I interferon pathway on disease activity, treatment, and outcomes. SPOCS recruitment and follow-up are ongoing. Disclosure of Interests Edward R. Hammond Employee of: AstraZeneca, Martin Aringer Grant/research support from: Roche, Consultant for: AstraZeneca and Eli Lilly, Laurent Arnaud Consultant for: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugai, and UCB., Paid instructor for: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugai, and UCB., Speakers bureau: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugai, and UCB., Christine Peschken Consultant for: AstraZeneca, Jacob Knagenhjelm Consultant for: I was employed by Dfind Science & Engineering working at AstraZeneca as a contractor statistician from late May 2017 - end April 2018, Employee of: AstraZeneca, Volkan Barut Employee of: AstraZeneca, Xia Wang Shareholder of: AstraZeneca, Employee of: AstraZeneca, Barnabas Desta Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca, David Ginkel Employee of: AstraZeneca, Richard Furie Grant/research support from: Biogen, UCB Pharma, but not in the last 12 months, Consultant for: Biogen, UCB Pharma, but not in the last 12 months, Eric F. Morand Grant/research support from: AstraZeneca, Bristol Myers Squibb, Janssen, Merck Serono, and UCB, Consultant for: AstraZeneca, Eli Lilly, Janssen, and Merck Serono, Speakers bureau: AstraZeneca

Thu0248 utility of a mobile phone based application to collect patient reported outcome information from subjects with systemic lupus erythematosus

Abstract: Background Patient Reported Outcomes (PROs) can provide important data about the impact of a disease on an individual subject and/or the quality of the response to medication. However, in most circumstances, PRO information is collected only intermittently and usually at the point of care or treatment. The development of mobile technology to collect PRO data provided the opportunity to acquire this information more frequently, in real time, and in the subject’s normal environment. Objectives To test the utility of a smart phone application (app) to collect PRO information in subjects with systemic lupus erythematosus (SLE). Methods A smart phone app was developed that collects data from a number of PRO instruments, including FACIT-F(fatigue), SF-36 (health-related quality of life) and patient global assessment (PtGA). Subjects with SLE were involved in the initial development and evaluation of the acceptability of the app. To test the utility of this app, a multi-center clinical study (VALUE, NCT03142711) was carried out in collaboration with subjects with SLE, in whom PRO information was collected with the app daily (PtGA) or weekly (FACIT-F and SF-36) in the subject’s environment and also with the app and a standard paper form monthly at each clinical site. Demographic information, compliance and intra-class correlation coefficients between information collected with the app and using a paper form at the clinical site were assessed. Results Of the 80 subjects enrolled in this study, 91.3% were women; 57.5%, 16.3% and 17.5% identified themselves as of European, African or Asian ancestry, respectively. The mean age of the subjects was 42.6 years and the mean duration of education was 15.6 years. Overall compliance with completing the PRO instruments with the app at the scheduled time was 88%. To determine the consistency of information collected with the app, PRO instruments were completed on three occasions: a) in standard fashion using a paper form and b) using the app, separated by an interruption at the clinical site. The mean (SD) PtGA scores at baseline, month 1 and month 2 were 3.3(2.4), 3.5(2.4) and 3.5(2.5) using the app and 3.2(2.4), 3.5(2.3) and 3.3(2.4) using the paper form. The Intraclass Correlation Coefficient (ICC) and 90%CI were 0.97 (0.96-0.98), 0.96 (0.94-0.97) and 0.95(0.93-0.97) at the three time points, respectively. For the FACIT-F instrument, the mean (SD) score with the app was 33.2(11.7), 31.0(12.6) and 32.3(12.7) and with the paper form was 34.1(11.6), 32.0(12.2) and 32.0(12.5) at the 3 time points with ICCs of 0.94(0.91-0.96), 0.96(0.95-0.98) and 0.96(0.94-0.97), respectively. For the SF-36 Physical Functioning score, the mean (SD) with the app was 66.3(26.1), 65.5(26.9) and 67.4(25.8) and with the paper form was 68.4(25.1), 66.1(26.6) and 67.6(25.8) for the 3 time points, respectively. The ICCs were 0.96(0.94-0.97), 0.94(0.91-0.96) and 0.96 (0.94-0.97) for the 3 time points, respectively. Conclusion Compliance with completion of PRO instruments using a mobile app was excellent and the content collected with the app conformed with that collected using a standard paper form. Since patient compliance with the use of a mobile app to collect PRO information and the consistency of the information obtained compared to that obtained in standard fashion using a paper form were high, the app affords the potential opportunity to acquire frequent and highly reliable information about the impact of disease and response to medication in individual subjects with SLE. Acknowledgement The study was sponsored by the Lupus Research Alliance and funded by Pfizer. Development and support of the app was provided by TCS. Disclosure of Interests Brooke Williams: None declared, Bridget Muckian: None declared, Christine Peschken Consultant for: AstraZeneca, Richard Furie Grant/research support from: Biogen, UCB Pharma, but not in the last 12 months, Consultant for: Biogen, UCB Pharma, but not in the last 12 months, Elena Massarotti: None declared, vanja sikirica Shareholder of: Pfizer, Employee of: Pfizer, Steven Gilbert Shareholder of: Pfizer, Employee of: Pfizer, Martin Hodge Shareholder of: Pfizer, Employee of: Pfizer, Peter Lipsky Consultant for: Consulting fees from Horizon Pharma