Faculty Bibliography

OBJECTIVE:Physical activity can reduce cardiovascular disease and depression risk and improve quality of life in patients with systemic lupus erythematosus (SLE). To facilitate physical activity and achieve health benefits in patients with SLE, it is critical to understand potential barriers to physical activity, including socioeconomic, social, demographic, quality-of-life, or clinical factors. METHODS:We conducted cross-sectional analyses of data from a large, diverse cohort of patients with SLE. All completed the International Physical Activity Questionnaire, recalling the past seven days of vigorous physical activity, moderate activity, or walking. Data included financial insecurity, Everyday Discrimination Scale, education, demographics, lupus-specific disease activity, immunosuppressive medication, Census Block Area Deprivation Index, and patient-reported pain, fatigue, and cognitive function. Multivariable models included logistic regression for dichotomous outcome of "any" moderate/vigorous physical activity and quasi-Poisson model for total combined days of moderate and vigorous activity. RESULTS:Of the 271 participants, 170 (63%) reported any moderate or vigorous activity in the past 7 days (mean = 2.6 days of moderate/vigorous activity). Only 4% reported zero days of physical activity. Logistic regression analysis indicated that active disease was associated with 47% lower odds of engaging in any moderate/vigorous physical activity (P = 0.04) and with a 35% reduction in the mean number of days of moderate to vigorous physical activity (P = 0.04). In contrast, individual- and area-level socioeconomic factors and patient-reported outcomes were not associated with physical activity. CONCLUSION/CONCLUSIONS:Moderate/vigorous physical activity was negatively associated only with disease activity. The current study reinforces the need primarily to control SLE disease activity to promote patients' ability to be physically active, which may improve symptoms.

BACKGROUND/UNASSIGNED:Hydroxychloroquine (HCQ) is a cornerstone of systemic lupus erythematosus (SLE) management. However, the medication can accumulate within organs and cause toxicity including retinopathy. HCQ is usually discontinued once ocular toxicity is diagnosed, but this is not always sufficient to avoid further damage. Whether retinal injury progresses following HCQ cessation, and which patients are at risk, is of great interest. Prior studies examining progression after HCQ discontinuation are sparse and limited by small sample sizes, and none specifically examine patients with SLE. This study aimed to identify predictors of progression of HCQ-induced retinopathy in SLE patients after medication discontinuation. METHODS/UNASSIGNED:We queried the NYU Lupus Cohort to identify patients with documented HCQ-induced retinopathy who discontinued HCQ and had at least one optical coherence tomography (OCT) follow-up to assess for progression. Demographic information, cumulative HCQ dose, duration of therapy, presence of chronic kidney disease or tamoxifen use, SLE disease activity, and ophthalmologic follow-up intervals were collected. Two ophthalmologists independently reviewed OCT and Humphrey visual field data to confirm retinopathy, grade its severity, and determine progression following drug discontinuation. Statistical analysis was performed using Student's t-test or Wilcoxon rank-sum test for continuous variables and Chi-square or Fisher's exact test for categorical variables. RESULTS/UNASSIGNED:Twenty-one patients with confirmed HCQ retinopathy were included. The mean duration of HCQ therapy preceding diagnosis was 16.2 years and the mean cumulative exposure was 1884 g. Retinal toxicity progressed in 6 patients (28.6%) despite HCQ discontinuation. There appeared to be a trend towards a greater likelihood of progression with more severe retinal toxicity at the time of diagnosis. However, there were no differences between progressors and non-progressors with respect to age at diagnosis, duration or cumulative HCQ exposure, SLE disease activity, tamoxifen use, chronic kidney disease, or guideline-concordant care. CONCLUSIONS/UNASSIGNED:Nearly thirty percent of patients with SLE and HCQ retinopathy progressed despite drug discontinuation. No baseline clinical predictors were associated with progression, though there was a descriptive trend toward greater risk with more severe baseline retinopathy. These data emphasize the importance of continued ocular surveillance for progression of toxicity after discontinuation.

ObjectivePatients with systemic lupus erythematosus (SLE) often have concomitant fibromyalgia (FM) or similar symptoms including chronic pain, fatigue, or depression. This study explored whether Patient-Reported Outcomes Measurement Information System (PROMIS) measures provide richer information than 2016 American College of Rheumatology (ACR) FM criteria survey.MethodsPatients with SLE in our convenience cohort were categorized into groups: (1) concurrent FM chronic pain, (2) concurrent non-FM chronic pain, and (3) no chronic pain using 2016 ACR FM Survey. Based on PROs in the FM Survey, we captured comparable PROMIS measures (e.g., depression, fatigue). Associations by pain group were tested using Kruskal-Wallis rank sum test, Shapiro-Wilk normality test, chi-squared test, or Fisher's exact test. Violin plots explored differences across groups.ResultsThe cohort (n = 181) included 31 patients with FM pain, 23 with non-FM chronic pain, and 127 with no chronic pain. Median PROMIS symptom scores (fatigue, sleep disturbance, pain intensity and interference, depression) were highest and cognitive function lowest in the FM group, despite 13% being in remission. There were significant differences on 4 PROMIS measures (cognitive function, fatigue, pain intensity, pain interference) between FM pain and non-FM pain groups (p < .02), the former being worse. There were no significant differences in SLE Disease Activity Index (SLEDAI) score.ConclusionSLE patients with non-FM chronic pain have similar symptoms to FM compared with SLE patients without chronic pain; however, symptoms are not as severe as those meeting FM criteria. PROMIS measures may be used to classify severity more precisely for disease categorization and management.

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/CONCLUSIONS: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.

OBJECTIVE:To evaluate seroreactivity and disease flares after COVID-19 vaccination in a multi-ethnic/racial cohort of patients with systemic lupus erythematosus (SLE). METHODS:90 SLE patients and 20 healthy controls receiving a complete COVID-19 vaccine regimen were included. IgG seroreactivity to the SARS-CoV-2 spike receptor-binding domain (RBD) and SARS-CoV-2 microneutralization were used to evaluate B cell responses; IFN-γ production to assess T cell responses was measured by ELISpot. Disease activity was measured by the hybrid SLE disease activity index (SLEDAI) and flares were assigned by the SELENA/SLEDAI flare index. RESULTS:Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS-CoV-2 spike RBD than controls. Twenty-six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti-dsDNA level prior to vaccination associated with decreased vaccine responses. IgG seroreactivity to the SARS-CoV-2 Spike RBD strongly correlated with the SARS-CoV-2 microneutralization titers and antigen-specific IFN-γ production determined by ELISpot. In a subset of patients with poor antibody responses, IFN-γ production was likewise diminished. Pre-/post-vaccination SLEDAI scores were similar. Only 11.4% of patients had a post-vaccination flare; 1.3% were severe. CONCLUSION/CONCLUSIONS:In a multi-ethnic/racial study of SLE patients 29% had a low response to the COVID-19 vaccine which was associated with being on immunosuppression. Reassuringly, disease flares were rare. While minimal protective levels remain unknown, these data suggest protocol development is needed to assess efficacy of booster vaccination.

BACKGROUND:Although hydroxychloroquine (HCQ) is a mainstay of treatment for patients with systemic lupus erythematosus (SLE), ocular toxicity can result from accumulated exposure. As the longevity of patients with SLE improves, data are needed to balance the risk of ocular toxicity and the risk of disease flare, especially in older patients with quiescent disease. Accordingly, this study was initiated to examine the safety of HCQ withdrawal in older SLE patients. METHODS:Data were obtained by retrospective chart review at three major lupus centers in New York City. Twenty-six patients who discontinued HCQ and thirty-two patients on HCQ matched for gender, race/ethnicity, and age were included in this study. The primary outcome was the occurrence of a lupus flare classified by the revised version of the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare composite index, within 1 year of HCQ withdrawal or matched time of continuation. RESULTS:Five patients (19.2%) in the HCQ withdrawal group compared to five (15.6%) in the HCQ continuation group experienced a flare of any severity (odds ratio [OR] = 1.28; 95% CI 0.31, 5.30; p = 0.73). There were no severe flares in either group. The results were similar after adjusting for length of SLE, number of American College of Rheumatology criteria, low complement levels, and SELENA-SLEDAI score, and in a propensity score analysis (OR = 1.18; 95% CI 0.23, 6.16; p = 0.84). The analysis of time to any flare revealed a non-significant earlier time to flare in the HCQ withdrawal group (log-rank p = 0.67). Most flares were in the cutaneous and musculoskeletal systems, but one patient in the continuation group developed pericarditis. The most common reason for HCQ withdrawal was retinal toxicity (42.3%), followed by patient's preference (34.6%), other confirmed or suspected adverse effects (15.4%), ophthalmologist recommendation for macular degeneration (3.8%), and rheumatologist recommendation for quiescent SLE (3.8%). CONCLUSIONS:In this retrospective study of older stable patients with SLE on long-term HCQ, withdrawal did not significantly increase the risk of flares.