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      Flares after hydroxychloroquine reduction or discontinuation: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort

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      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 1 , 39 ,
      Annals of the Rheumatic Diseases
      BMJ Publishing Group
      systemic lupus erythematosus, hydroxychloroquine, autoimmune diseases, epidemiology

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          Abstract

          Objectives

          To evaluate systemic lupus erythematosus (SLE) flares following hydroxychloroquine (HCQ) reduction or discontinuation versus HCQ maintenance.

          Methods

          We analysed prospective data from the Systemic Lupus International Collaborating Clinics (SLICC) cohort, enrolled from 33 sites within 15 months of SLE diagnosis and followed annually (1999–2019). We evaluated person-time contributed while on the initial HCQ dose (‘maintenance’), comparing this with person-time contributed after a first dose reduction, and after a first HCQ discontinuation. We estimated time to first flare, defined as either subsequent need for therapy augmentation, increase of ≥4 points in the SLE Disease Activity Index-2000, or hospitalisation for SLE. We estimated adjusted HRs (aHRs) with 95% CIs associated with reducing/discontinuing HCQ (vs maintenance). We also conducted separate multivariable hazard regressions in each HCQ subcohort to identify factors associated with flare.

          Results

          We studied 1460 (90% female) patients initiating HCQ. aHRs for first SLE flare were 1.20 (95% CI 1.04 to 1.38) and 1.56 (95% CI 1.31 to 1.86) for the HCQ reduction and discontinuation groups, respectively, versus HCQ maintenance. Patients with low educational level were at particular risk of flaring after HCQ discontinuation (aHR 1.43, 95% CI 1.09 to 1.87). Prednisone use at time-zero was associated with over 1.5-fold increase in flare risk in all HCQ subcohorts.

          Conclusions

          SLE flare risk was higher after HCQ taper/discontinuation versus HCQ maintenance. Decisions to maintain, reduce or stop HCQ may affect specific subgroups differently, including those on prednisone and/or with low education. Further study of special groups (eg, seniors) may be helpful.

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          Most cited references47

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          Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus

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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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              2019 update of the EULAR recommendations for the management of systemic lupus erythematosus

              Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007–12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.
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                Author and article information

                Journal
                Ann Rheum Dis
                Ann Rheum Dis
                annrheumdis
                ard
                Annals of the Rheumatic Diseases
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0003-4967
                1468-2060
                March 2022
                15 December 2021
                : 81
                : 3
                : 370-378
                Affiliations
                [1 ] departmentDivision of Clinical Epidemiology , Research Institute of the McGill University Health Centre , Montreal, Quebec, Canada
                [2 ] departmentDivision of Rheumatology, Department of Medicine and Department of Pathology , Queen Elizabeth II Health Sciences Centre , Halifax, Nova Scotia, Canada
                [3 ] departmentCenter for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital , University of Toronto , Toronto, Ontario, Canada
                [4 ] departmentDivisions of Clinical Immunology/Allergy and Clinical Epidemiology , University of Calgary , Calgary, Alberta, Canada
                [5 ] departmentAutoimmune Diseases Unit , Hospital Universitario Cruces , Barakaldo, País Vasco, Spain
                [6 ] departmentRheumatology Research Group , University of Birmingham , Birmingham, UK
                [7 ] departmentMedicine/Rheumatology , Northwestern University , Evanston, Illinois, USA
                [8 ] departmentRheumatology , Johns Hopkins University , Baltimore, Maryland, USA
                [9 ] departmentMedicine/Rheumatology , SUNY Downstate Medical Center , New York City, New York, USA
                [10 ] departmentCedars-Sinai/David Geffen School of Medicine at UCLA , Cedars-Sinai Medical Center , Los Angeles, California, USA
                [11 ] departmentRheumatology , Hanyang University , Seongdong-gu, Seoul, The Republic of Korea
                [12 ] departmentImmunology and Rheumatology , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran , Ciudad de Mexico, Mexico
                [13 ] departmentMedicine , Unversity of North Carolina , Chapel Hill, North Carolina, USA
                [14 ] departmentDivision of Rheumatology , University of Manitoba , Winnipeg, Manitoba, Canada
                [15 ] departmentDivision of Medicine , University College London , London, UK
                [16 ] departmentRheumatology , University College London , London, UK
                [17 ] departmentAllegheny Singer Research Institute , Allegheny Health Network , Pittsburgh, Pennsylvania, USA
                [18 ] departmentCopenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases , Rigshospitalet , Copenhagen, Denmark
                [19 ] departmentSchool of Medicine , Emory University , Atlanta, Georgia, USA
                [20 ] departmentDepartment of Rheumatology , Amsterdam Rheumatology and Immunology Center , Amsterdam, The Netherlands
                [21 ] departmentRheumatology , Lund University , Lund, Sweden
                [22 ] departmentFaculty of Medicine, Department of Clinical Sciences Lund, Section of Rheumatology , Lund University , Lund, Sweden
                [23 ] Medical University of South Carolina , Charleston, South Carolina, USA
                [24 ] Northwell Health Feinstein Institutes for Medical Research Institute of Health Innovations and Outcomes Research , Manhasset, New York, USA
                [25 ] departmentCenter for Prognosis Studies in the Rheumatic Diseases , Toronto Western Hospital , Toronto, Ontario, Canada
                [26 ] University of Toronto , Toronto, Ontario, Canada
                [27 ] departmentMedicine—Rheumatology , Université Laval , Quebec, Quebec, Canada
                [28 ] departmentDepartment of Medicine, Division of Clinical Immunology and Rheumatology , University of Alabama at Birmingham Center for Health Promotion , Birmingham, Alabama, USA
                [29 ] departmentArthritis and Clinical Immunology Program , Oklahoma Medical Research Foundation , Oklahoma City, Oklahoma, USA
                [30 ] departmentDivision of Rheumatology, Allergy and Immunology , University of California San Diego School of Medicine , La Jolla, California, USA
                [31 ] departmentDepartment of Autoimmune Diseases , Universitat de Barcelona , Barcelona, Catalunya, Spain
                [32 ] departmentRheumatology, Department of Obstetrics and Gynecology , Landspitali University Hospital , Reyjavik, Iceland
                [33 ] departmentLanarkshire Centre for Rheumatology , Hairmyres Hospital , East Kilbride, South Lanarkshire, UK
                [34 ] departmentRheumatology , Columbia University Medical Center , New York, New York, USA
                [35 ] departmentThe Rayne Institute, St Thomas Hospital , St Thomas' Hospital , London, UK
                [36 ] departmentArc Epidemiology Unit , The University of Manchester , Manchester, UK
                [37 ] departmentDepartment of Internal Medicine, Division of Rheumatology , Istanbul University , Fatih, Istanbul, Turkey
                [38 ] departmentDepartment of Epidemiology Biostatistics and Occupational Health , McGill University , Montreal, Quebec, Canada
                [39 ] departmentDivision of Rheumatology , McGill University Health Centre , Montreal, Quebec, Canada
                Author notes
                [Correspondence to ] Dr Sasha Bernatsky, Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; sasha.bernatsky@ 123456mcgill.ca
                Author information
                http://orcid.org/0000-0003-1029-9483
                http://orcid.org/0000-0001-7506-9166
                http://orcid.org/0000-0001-7788-1043
                http://orcid.org/0000-0003-1441-5373
                http://orcid.org/0000-0003-4658-1093
                http://orcid.org/0000-0001-9514-2455
                http://orcid.org/0000-0003-2346-4484
                http://orcid.org/0000-0002-5654-4993
                http://orcid.org/0000-0001-6438-8663
                http://orcid.org/0000-0001-9299-0053
                http://orcid.org/0000-0002-9074-0592
                http://orcid.org/0000-0002-7278-2596
                http://orcid.org/0000-0001-5190-9175
                http://orcid.org/0000-0001-5709-6734
                http://orcid.org/0000-0002-6376-5583
                http://orcid.org/0000-0002-9515-2802
                Article
                annrheumdis-2021-221295
                10.1136/annrheumdis-2021-221295
                8862090
                34911705
                ef2e7c65-ac35-4f18-9d50-30fe0ab1e78a
                © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

                History
                : 06 August 2021
                : 10 November 2021
                Funding
                Funded by: National Institute for Health Research (NIHR)/Wellcome Trust;
                Award ID: N/A
                Funded by: FundRef http://dx.doi.org/10.13039/100008368, Gigtforeningen;
                Award ID: A3865
                Funded by: FundRef http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;
                Award ID: NRF-2017M3A9B4050335
                Funded by: Birmingham Clinical Research Facility;
                Award ID: N/A
                Funded by: FundRef http://dx.doi.org/10.13039/501100000142, Arthritis Society;
                Award ID: N/A
                Funded by: FundRef http://dx.doi.org/10.13039/100011327, Sandwell and West Birmingham Hospitals NHS Trust;
                Award ID: N/A
                Funded by: Montreal General Hospital;
                Award ID: N/A
                Funded by: FundRef http://dx.doi.org/10.13039/100008459, University of Calgary;
                Award ID: N/A
                Funded by: Manchester Clinical Research Facility;
                Award ID: N/A
                Funded by: FundRef http://dx.doi.org/10.13039/501100000272, National Institute for Health Research;
                Award ID: N/A
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: 5UL1TR001422–02
                Award ID: AR-43727
                Award ID: AR-69572
                Award ID: K24-AR-02318
                Award ID: P60AR064464
                Award ID: RR00046
                Award ID: UL-1RR-025741
                Funded by: FundRef http://dx.doi.org/10.13039/501100004191, Novo Nordisk;
                Award ID: A05990
                Funded by: Fonds de Recherche du Québec Santé (FRQS);
                Award ID: N/A
                Funded by: NHS;
                Award ID: N/A
                Funded by: Canadian Institutes of Health Research (CIHR);
                Award ID: N/A
                Funded by: Research Institute of the McGill University Health Centre;
                Award ID: N/A
                Funded by: National Institute for Health Research (NIHR);
                Award ID: N/A
                Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: N/A
                Funded by: FundRef http://dx.doi.org/10.13039/100000030, Centers for Disease Control and Prevention;
                Award ID: U01DP005119
                Funded by: FundRef http://dx.doi.org/10.13039/501100000341, Arthritis Research UK;
                Award ID: N/A
                Categories
                Systemic Lupus Erythematosus
                1506
                2311
                2200
                2494
                Custom metadata
                unlocked

                Immunology
                systemic lupus erythematosus,hydroxychloroquine,autoimmune diseases,epidemiology
                Immunology
                systemic lupus erythematosus, hydroxychloroquine, autoimmune diseases, epidemiology

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