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      Flares in patients with systemic lupus erythematosus

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          Abstract

          Objective

          SLE is characterized by relapses and remissions. We aimed to describe the frequency, type and time to flare in a cohort of SLE patients.

          Methods

          SLE patients with one or more ‘A’ or ‘B’ BILAG-2004 systems meeting flare criteria (‘new’ or ‘worse’ items) and requiring an increase in immunosuppression were recruited from nine UK centres and assessed at baseline and monthly for 9 months. Subsequent flares were defined as: severe (any ‘A’ irrespective of number of ‘B’ flares), moderate (two or more ‘B’ without any ‘A’ flares) and mild (one ‘B’).

          Results

          Of the 100 patients, 94% were female, 61% White Caucasians, mean age ( s. d.) was 40.7 years (12.7) and mean disease duration ( s. d.) was 9.3 years (8.1). A total of 195 flares re-occurred in 76 patients over 781 monthly assessments (flare rate of 0.25/patient-month). There were 37 severe flares, 32 moderate flares and 126 mild flares. By 1 month, 22% had a mild/moderate/severe flare and 22% had a severe flare by 7 months. The median time to any ‘A’ or ‘B’ flare was 4 months. Severe/moderate flares tended to be in the system(s) affected at baseline, whereas mild flares could affect any system.

          Conclusion

          . In a population with active SLE we observed an ongoing rate of flares from early in the follow-up period with moderate–severe flares being due to an inability to fully control the disease. This real-world population study demonstrates the limitations of current treatments and provides a useful reference population from which to inform future clinical trial design.

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          Most cited references32

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          Systemic lupus erythematosus disease activity index 2000.

          To describe the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), a modification of SLEDAI to reflect persistent, active disease in those descriptors that had previously only considered new or recurrent occurrences, and to validate SLEDAI-2K against the original SLEDAI as a predictor for mortality and as a measure of global disease activity in the clinic. All visits in our cohort of 960 patients were used to correlate SLEDAI-2K against the original SLEDAI, and the whole cohort was used to validate SLEDAI-2K as a predictor of mortality. A subgroup of 212 patients with SLE followed at the Lupus Clinic who had 5 regular visits, 3-6 months apart, in 1991-93 was also included. An uninvolved clinician evaluated each patient record and assigned a clinical activity level. The SLEDAI score was calculated from the database according to both the original and modified definitions. SLEDAI-2K correlated highly (r = 0.97) with SLEDAI. Both methods for SLEDAI scoring predicted mortality equally (p = 0.0001), and described similarly the range of disease activity as recognized by the clinician. SLEDAI-2K, which allows for persistent activity in rash, mucous membranes, alopecia, and proteinuria, is suitable for use in clinical trials and studies of prognosis in SLE.
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            Combined oral contraceptives in women with systemic lupus erythematosus.

            Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double-blind, randomized, noninferiority trial, we prospectively evaluated the effect of oral contraceptives on lupus activity in premenopausal women with systemic lupus erythematosus. A total of 183 women with inactive (76 percent) or stable active (24 percent) systemic lupus erythematosus at 15 U.S. sites were randomly assigned to receive either oral contraceptives (triphasic ethinyl estradiol at a dose of 35 microg plus norethindrone at a dose of 0.5 to 1 mg for 12 cycles of 28 days each; 91 women) or placebo (92 women) and were evaluated at months 1, 2, 3, 6, 9, and 12. Subjects were excluded if they had moderate or high levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis. The primary end point, a severe lupus flare, occurred in 7 of 91 subjects receiving oral contraceptives (7.7 percent) as compared with 7 of 92 subjects receiving placebo (7.6 percent). The 12-month rates of severe flare were similar: 0.084 for the group receiving oral contraceptives and 0.087 for the placebo group (P=0.95; upper limit of the one-sided 95 percent confidence interval for this difference, 0.069, which is within the prespecified 9 percent margin for noninferiority). Rates of mild or moderate flares were 1.40 flares per person-year for subjects receiving oral contraceptives and 1.44 flares per person-year for subjects receiving placebo (relative risk, 0.98; P=0.86). In the group that was randomized to receive oral contraceptives, there was one deep venous thrombosis and one clotted graft; in the placebo group, there was one deep venous thrombosis, one ocular thrombosis, one superficial thrombophlebitis, and one death (after cessation of the trial). Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable. Copyright 2005 Massachusetts Medical Society.
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              Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort

              Background and aims We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients. Methods The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan–Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality. Results We recruited 1722 patients; mean (SD) age 35.0 (13.4) years at cohort entry. Patients with damage at enrolment were more likely to have further worsening of SDI (SDI 0 vs ≥1; p<0.001). Age, USA African race/ethnicity, SLEDAI-2K score, steroid use and hypertension were associated with transition from no damage to damage, and increase(s) in pre-existing damage. Male gender (relative transition rates (95% CI) 1.48 (1.06 to 2.08)) and USA Caucasian race/ethnicity (1.63 (1.08 to 2.47)) were associated with SDI 0 to ≥1 transitions; Asian race/ethnicity patients had lower rates of new damage (0.60 (0.39 to 0.93)). Antimalarial use was associated with lower rates of increases in pre-existing damage (0.63 (0.44 to 0.89)). Damage was associated with future mortality (HR (95% CI) 1.46 (1.18 to 1.81) per SDI point). Conclusions Damage in SLE predicts future damage accrual and mortality. We identified several potentially modifiable risk factors for damage accrual; an integrated strategy to address these may improve long-term outcomes.
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                Author and article information

                Journal
                Rheumatology (Oxford)
                Rheumatology (Oxford)
                brheum
                Rheumatology (Oxford, England)
                Oxford University Press
                1462-0324
                1462-0332
                July 2021
                16 December 2020
                16 December 2020
                : 60
                : 7
                : 3262-3267
                Affiliations
                [1 ]Department of Rheumatology, Royal Blackburn Hospital, Haslingden Road , Blackburn
                [2 ] School of Psychology
                [3 ]Faculty of Health and Wellbeing, University of Central Lancashire , Preston
                [4 ] Rheumatology, Nottingham University Hospitals NHS Trust
                [5 ]Epidemiology and Public Health, University of Nottingham , Nottingham
                [6 ]NIHR Nottingham Biomedical Research Centre , Nottingham
                [7 ]Centre for Rheumatology Research, University College London, The Rayne Building, 4th Floor, 5 University Street , London
                [8 ]Department of Rheumatology, Doncaster Royal Infirmary, Armthorpe Road , Doncaster
                [9 ]Department of Rheumatology, Royal Hallamshire Hospital, Glossop Road , Sheffield
                [10 ]Arthritis Research UK Centre for Epidemiology, Faculty of Biology, Medicine and Health, The University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre , Manchester
                [11 ]Peter Maddison Rheumatology Centre, Betsi Cadwaldr University Health Board, Llandudno Hospital, Llandudno , Conwy
                [12 ]Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences , University of Birmingham
                [13 ] Rheumatology Department, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust
                [14 ] NIHR/Wellcome Trust Birmingham Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham
                [15 ] Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK
                Author notes
                Correspondence to: Lee-Suan Teh, Department of Rheumatology, N2222 Mezzanine Floor, Royal Blackburn Teaching Hospital, Haslingden Road, Blackburn BB2 3HH, UK. E-mail: lsteh@ 123456btinternet.com
                Author information
                https://orcid.org/0000-0003-2346-4484
                Article
                keaa777
                10.1093/rheumatology/keaa777
                8517882
                33325488
                c9645f66-31eb-4987-ab38-9604eb13d2e2
                © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 January 2020
                : 14 October 2020
                Page count
                Pages: 6
                Funding
                Funded by: Arthritis Research UK, DOI 10.13039/501100000341;
                Award ID: 19230
                Categories
                Clinical Science
                AcademicSubjects/MED00360

                Rheumatology
                flares,disease activity,bilag-2004 index,sle
                Rheumatology
                flares, disease activity, bilag-2004 index, sle

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