Breakthrough SARS-CoV-2 infections, morbidity, and seroreactivity following initial COVID-19 vaccination series and additional dose in patients with SLE in New York City
Saxena, Amit; Engel, Alexis J; Banbury, Brittany; Hasan, Ghadeer; Fraser, Nicola; Zaminski, Devyn; Masson, Mala; Haberman, Rebecca H; Scher, Jose U; Ho, Gary; Law, Jammie; Rackoff, Paula; Tseng, Chung-E; Belmont, H Michael; Clancy, Robert M; Buyon, Jill P; Izmirly, Peter M
Evaluation of Immune Response and Disease Status in SLE Patients Following SARS-CoV-2 Vaccination
Izmirly, Peter M; Kim, Mimi Y; Samanovic, Marie; Fernandez-Ruiz, Ruth; Ohana, Sharon; Deonaraine, Kristina K; Engel, Alexis J; Masson, Mala; Xie, Xianhong; Cornelius, Amber R; Herati, Ramin S; Haberman, Rebecca H; Scher, Jose U; Guttmann, Allison; Blank, Rebecca B; Plotz, Benjamin; Haj-Ali, Mayce; Banbury, Brittany; Stream, Sara; Hasan, Ghadeer; Ho, Gary; Rackoff, Paula; Blazer, Ashira D; Tseng, Chung-E; Belmont, H Michael; Saxena, Amit; Mulligan, Mark J; Clancy, Robert M; Buyon, Jill P
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-Î³ 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-Î³ production determined by ELISpot. In a subset of patients with poor antibody responses, IFN-Î³ 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.
Discontinuation of hydroxychloroquine in older patients with systemic lupus erythematosus: a multicenter retrospective study
Fernandez-Ruiz, Ruth; Bornkamp, Nicole; Kim, Mimi Y; Askanase, Anca; Zezon, Anna; Tseng, Chung-E; Belmont, H Michael; Saxena, Amit; Salmon, Jane E; Lockshin, Michael; Buyon, Jill P; Izmirly, Peter M
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 1Â 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]â€‰=â€‰1.28; 95% CI 0.31, 5.30; pÂ =â€‰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 (ORâ€‰=â€‰1.18; 95% CI 0.23, 6.16; pÂ =â€‰0.84). The analysis of time to any flare revealed a non-significant earlier time to flare in the HCQ withdrawal group (log-rank pÂ =â€‰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.
Safety of Hydroxychloroquine Withdrawal in Older Adults with Systemic Lupus Erythematosus [Meeting Abstract]
Zezon, Anna; Izmirly, Peter M; Bornkamp, Nicole; Tseng, Chung-E; Belmont, HMichael; Askanase, Anca; Salmon, Jane E; Lockshin, Michael; Buyon, Jill P
Favorable Clinical Response To Belimumab At Three Months [Meeting Abstract]
Askanase, Anca ; Reddy, Arthi ; Buyon, Jill P. ; Franks, Andrew G., Jr. ; Furie, Richard A. ; Kamen, Diane L. ; Manzi, Susan ; Petri, Michelle ; Ramsey-Goldman, Rosalind ; Tseng, Chung-E ; van Vollenhoven, Ronald F. ; Wallace, Daniel J.
Favorable Response to Belimumab At Three Months [Meeting Abstract]
Shum, Katrina M.; Buyon, Jill P.; Belmont, H. Michael; Franks, Andrew G.; Furie, Richard; Kamen, Diane L.; Manzi, Susan; Petri, Michelle; Ramsey-Goldman, Rosalind; Tseng, Chung-E; van Vollenhoven, Ronald F.; Wallace, Daniel; Askanase, Anca
Association between myasthaenia gravis and systemic lupus erythematosus: three case reports and review of the literature [Review]
Castrejon, I.; Shum, K.; Tseng, C-E; Askanase, A.
The coexistence of systemic lupus erythematosus (SLE) and myasthaenia gravis (MG) has been reported previously. Because of their shared clinical characteristics and autoantibody-mediated pathogenesis, an SLE expert panel decided to include MG as one of the 19 neuropsychiatric SLE syndromes. This study reports a cluster of three cases of SLE/MG overlap from our cohort and a review of the published data concerning this overlap of SLE and MG. A systematic Medline review revealed 13 cases described in eight publications from 1994 to 2009. In summary, 12 of the 16 patients (three from our cohort and 13 from the reported cases) were women with an average age of 34 years. The most common SLE manifestations were polyarthritis (15 out of 16 patients), skin rashes (5/16), serositis (5/16), and cytopaenias (10/16). All of the patients were anti-nuclear antibodies (ANA) positive and 15/16 were anti-dsDNA positive. Proximal muscle weakness was the most frequent MG-related symptom (9/16), while 11/16 patients were anti-acetylcholine receptor (anti-AChR) antibody positive and 9/16 had diagnostic electromyography (EMG). These data suggest that MG should to be included in the differential diagnosis of lupus patients with fatigue and muscular weakness together with inflammatory and drug-induced myopathy
Clues To differentiate non-inflammatory from inflammatory symptoms in patients with Systemic Lupus erythematosus (SLE), using a multi-dimensional health assessment questionnaire (MDHAQ) [Meeting Abstract]
Pincus T.; Castrejon I.; Buyon J.P.; Tseng C.-E.; Izmirly P.M.; Yazici Y.; Askanase A.D.
Purpose: To analyze whether quantitative scores on a multidimensional health assessment questionnaire (MDHAQ) provide clues to the likelihood of inflammatory versus non-inflammatory symptoms and concomitant fibromyalgia, an important challenge in clinical care, according to a global scale for noninflammatory symptoms completed by a rheumatologist in 50 patients with SLE seen in usual care. Methods: A cross-sectional study was performed in 50 consecutive SLE patients of one rheumatologist seen in usual care. On arrival at the clinic, patients completed a multidimensional health assessment questionnaire (MDHAQ) which includes scales for physical function (FN), 0-10 visual analog scales for pain (PN), global estimate (PTGL) and fatigue (FT), and a review of systems symptom checklist (SX). SLE patients also completed a self-report Systemic Lupus Assessment Questionnaire (SLAQ). The rheumatologist, unaware of MDHAQ and SLAQ scores, recorded a physician global estimate (MDGL) and an estimate of non-inflammatory symptoms, each scored on a 0-3 scale in 0.1 increments, as well as four SLE indices: SLEDAI-2K (SLE Disease Activity Index), BILAG (British Isles Lupus Assessment Group index), SLAM (SLE Activity Measure) with and without laboratory tests, and ECLAM (European Consensus Lupus Activity Measurement). SLE patients with scores of <0.5 on the noninflammatory symptom scale were regarded as low and those with scores >=0.5 high noninflammatory symptoms; the two groups were compared using the Mann-Whitney statistic. Results: The study included 45 women and 5 men, mean age 38.7 years, mean disease duration 7.3 years. Of the 50 patients, 16 had high and 34 low scores for non-inflammatory symptoms. Those with high scores for non-inflammatory symptoms had significantly higher scores for FN, PN, FT, PTGL, SX, SLAQ, and SLAM without laboratory tests, as well as significantly lower CRP. No significant differences were seen patients estimated as high and low scoring patients for SLEDAI, BILAG, SLAM, ECLAM, C3, C4, antiDsDNA, or ESR. Fewer than 50% of low patients had FN, PN, PTGL, or FT >=2, while 100% of high patients had FT >2, and 94% PTGL >2. All patients with high non-inflammatory symptoms (16/16) reported more than 5 SX, compared to 15/34 (44%) low patients, and 12/16 (75%) high patients reported >10 SX, compared to 6/34 (18%) low patients. (Table Presented) Conclusion: High scores for dysfunction, pain, fatigue, global estimates, and number of symptoms are common in SLE patients with high versus low levels of non-inflammatory symptoms. SLE indices do not distinguish between patients with high versus low levels of non-inflammatory symptoms. A simple global scale to estimate non-inflammatory symptoms may be informative in therapeutic decisions, particularly if consistent with patient questionnaire patterns
Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis
Izmirly, Peter M; Barisoni, Laura; Buyon, Jill P; Kim, Mimi Y; Rivera, Tania L; Schwartzman, Julie S; Weisstuch, Joseph M; Liu, David T; Bernstein, Stephen; Tseng, Chung-E; Belmont, Howard M; Esmon, Charles T; Merrill, Joan T; Askanase, Anca D; Thomas, David B; Clancy, Robert M
OBJECTIVE: To study the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in lupus nephritis (LN) as a potential marker of injury and/or prognostic indicator for response to therapy. METHODS: mEPCR expression was analysed by immunohistochemistry in normal kidney and in 59 biopsies from 49 patients with LN. Clinical parameters were assessed at baseline, 6 months and 1 year. RESULTS: mEPCR was expressed in the medulla, arterial endothelium and cortical peritubular capillaries (PTCs) in all biopsies with LN but not in the cortical PTCs of normal kidney. Positive mEPCR staining in >25% of the PTCs was observed in 16/59 biopsies and associated with poor response to therapy. Eleven (84.6%) of 13 patients with positive staining for mEPCR in >25% of the PTCs and follow-up at 6 months did not respond to therapy, compared with 8/28 (28.6%) with mEPCR staining in < or =25% PTCs, P = 0.0018. At 1 year, 10 (83.3%) of 12 patients with positive mEPCR staining in >25% of the PTCs did not respond to therapy (with two progressing to end-stage renal disease) compared with 8/24 (33.3%) with positive staining in < or =25% of the PTCs, P = 0.0116. Although tubulo-interstitial damage (TID) was always accompanied by mEPCR, this endothelial marker was extensively expressed in the absence of TID suggesting that poor response could not be attributed solely to increased TID. mEPCR expression was independent of International Society of Nephrology/Renal Pathology Society class, activity and chronicity indices. CONCLUSION: Increased mEPCR expression in PTCs may represent a novel marker of poor response to therapy for LN
Current therapies for lupus nephritis in an ethnically heterogeneous cohort
Rivera, Tania L; Belmont, H Michael; Malani, Seema; Latorre, Melissa; Benton, Lauri; Weisstuch, Joseph; Barisoni, Laura; Tseng, Chung-E; Izmirly, Peter M; Buyon, Jill P; Askanase, Anca D
OBJECTIVE: To evaluate responses to mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC) in lupus nephritis in a multiethnic population. METHODS: This was a retrospective study of all patients with systemic lupus erythematosus (SLE) that underwent kidney biopsy at New York University Medical Center. Patients with followup of at least 6 months were included. Clinical response was defined as complete (return to +/- 10% of normal) or partial (improvement of 50% in abnormal renal measurements). RESULTS: Ninty-nine patients were included in the study: 86% females, 86% non-Caucasian, age 34.2 +/- 1.1 years, 62% with proliferative nephritis (PN; ISN/RPS-III and IV), and 32% with membranous nephritis (MN; ISN/RPS-V). Of the 70 patients with PN, 37 were treated with CYC and 33 with MMF. The baseline characteristics of the 2 treatment groups were different in the incidence of ISN/RPS-IV, values of serum creatinine and serum albumin, and type of insurance (p < 0.05). The response rate was greater in the MMF than in the CYC group (70% vs 41%). Responses to MMF were different in Asians (11/11), Caucasians (4/5), African Americans (3/5), and Hispanics (5/11). Responses to CYC had a similar distribution (Asians 6/10, Caucasians 4/5, African Americans 4/9, Hispanics 1/11). In the MN group (N = 23) responses were similar to the PN group (73% MMF and 38% CYC). After adjusting for race, serum creatinine, serum albumin, type of insurance, and class of nephritis, in a logistic regression model, response to MMF was superior to CYC: OR 6.2 (95% CI 1.9-20.2). Hispanics had worse outcome than Caucasians (OR 0.17). Longterm followup suggested no difference in maintenance with MMF or CYC. CONCLUSION: After controlling for the fact that less severe nephritis is preferentially treated with MMF, we found overall that response to MMF was superior to CYC. In this US population, ethnicity was observed to have an influence on response