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      Comparing the burdens of opportunistic infections among patients with systemic rheumatic diseases: a nationally representative cohort study

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          Abstract

          Objective

          To estimate and compare the burdens of opportunistic infections and herpes zoster in real-world practice among patients with various systemic rheumatic diseases.

          Methods

          This 13-year cohort study used national health insurance data to compare the incidence rates (IRs) of nine opportunistic infections among patients with five rheumatic diseases. The analyses were stratified according to follow-up duration using Poisson regression, and Cox models were used to compare the risk of first opportunistic infection.

          Results

          During 2000–2013, we identified 76,966 patients who had polymyositis/dermatomyositis (PM/DM, 2270 cases), systemic lupus erythematosus (SLE, 15,961 cases), systemic sclerosis (SSc, 2071 cases), rheumatoid arthritis (RA, 38,355 cases), or primary Sjögren’s syndrome (pSS, 18,309 cases). The IR of opportunistic infections was highest for PM/DM cases (61.3/1000 person-years, 95% confidence interval [CI] 56.6–66.2), followed by SLE cases (43.1/1000 person-years, 95% CI 41.7–44.5), SSc cases (31.6/1000 person-years, 95% CI 28.3–35.1), RA cases (25.0/1000 person-years, 95% CI 24.4–25.7), and pSS cases (24.1/1000 person-years, 95% CI 23.1–25.2). Multivariable Cox analysis revealed that, relative to SLE, PM/DM was associated with a significantly higher risk of opportunistic infections (hazard ratio 1.18, 95% CI 1.08–1.29). The risk of opportunistic infections was highest during the first year after the diagnosis of all five rheumatic diseases.

          Conclusions

          The risk of opportunistic infection was highest for PM/DM, followed by SLE, SSc, RA, and pSS. Careful observation and preventive therapy for opportunistic infections may be warranted in selected PM/DM patients, especially during the first year after the diagnosis.

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          Most cited references33

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          Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies.

          Infection is one of the leading causes of morbidity and mortality in systemic lupus erythematosus (SLE). Bacterial infections are most frequent, followed by viral and fungal infections. The impaired cellular and humoral immune functions seen in patients with SLE are predisposing conditions, whilst disease activity, prednisone doses over 7.5-10 mg/day, high doses of methylprednisolone or cyclophosphamide are well-recognised risk factors for infection. The first six months after rituximab treatment and the use of more than three courses are also associated with an increased susceptibility for infection. It has not been established whether belimumab, azathioprine and mycophenolate mofetil increase the risk of serious infections. Most vaccines are effective and safe in SLE patients, although vaccination should be avoided during periods of active disease. Live virus vaccines are contraindicated for immunosuppressed patients. Influenza and pneumococcal vaccines are universally recommended. Tuberculosis prophylaxis should be considered in selected cases. Therefore, it is advisable not to exceed doses of 5 mg/day of prednisone in chronic treatment. Methylprednisolone and cyclophosphamide should be used in low-dose regimens. Antimalarials have a well-known protective role against infection, in addition to other beneficial properties, thus, hydroxychloroquine is recommended for all SLE patients where no contraindication exists.
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            Serious infections among adult Medicaid beneficiaries with systemic lupus erythematosus and lupus nephritis.

            To examine the epidemiology of serious infections, a significant cause of morbidity and mortality in systemic lupus erythematosus (SLE), in a nationwide cohort of SLE and lupus nephritis (LN) patients.
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              Risk of serious infections in tocilizumab versus other biologic drugs in patients with rheumatoid arthritis: a multidatabase cohort study

              To investigate the rate of serious bacterial, viral or opportunistic infection in patients with rheumatoid arthritis (RA) starting tocilizumab (TCZ) versus tumour necrosis factor inhibitors (TNFi) or abatacept. Using claims data from US Medicare from 2010 to 2015, and IMS and MarketScan from 2011 to 2015, we identified adults with RA who initiated TCZ or TNFi (primary comparator)/abatacept (secondary comparator) with prior use of ≥1 different biologic drug or tofacitinib. The primary outcome was hospitalised serious infection (SI), including bacterial, viral or opportunistic infection. To control for >70 confounders, TCZ initiators were propensity score (PS)-matched to TNFi or abatacept initiators. Database-specific HRs were combined by a meta-analysis. The primary cohort included 16 074 TCZ PS-matched to 33 109 TNFi initiators. The risk of composite SI was not different between TCZ and TNFi initiators (combined HR 1.05, 95% CI 0.95 to 1.16). However, TCZ was associated with an increased risk of serious bacterial infection (HR 1.19, 95% CI 1.07 to 1.33), skin and soft tissue infections (HR 2.38, 95% CI 1.47 to 3.86), and diverticulitis (HR 2.34, 95% CI 1.64 to 3.34) versus TNFi. An increased risk of composite SI, serious bacterial infection, diverticulitis, pneumonia/upper respiratory tract infection and septicaemia/bacteraemia was observed in TCZ versus abatacept users. This large multidatabase cohort study found no difference in composite SI risk in patients with RA initiating TCZ versus TNFi after failing ≥1 biologic drug or tofacitinib. However, the risk of serious bacterial infection, skin and soft tissue infections, and diverticulitis was higher in TCZ versus TNFi initiators. The risk of composite SI was higher in TCZ initiators versus abatacept.
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                Author and article information

                Contributors
                chungyuango@gmail.com
                kochbye@gmail.com
                jiunlingwang@gmail.com
                htc@csmu.edu.tw
                +886-6-2353535 , linchunyumed@gmail.com
                Journal
                Arthritis Res Ther
                Arthritis Res. Ther
                Arthritis Research & Therapy
                BioMed Central (London )
                1478-6354
                1478-6362
                12 October 2019
                12 October 2019
                2019
                : 21
                : 211
                Affiliations
                [1 ]GRID grid.145695.a, Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, , Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, ; Kaohsiung, Taiwan
                [2 ]ISNI 0000 0004 0532 3749, GRID grid.260542.7, Department of Life Sciences, , National Chung Hsing University, ; Taichung, Taiwan
                [3 ]Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Yunlin, Taiwan
                [4 ]ISNI 0000 0004 0532 3255, GRID grid.64523.36, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, , National Cheng Kung University, ; No.138, Sheng Li Road, 704 Tainan, Taiwan
                [5 ]ISNI 0000 0004 0532 2041, GRID grid.411641.7, Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, ; Taichung, Taiwan
                Author information
                http://orcid.org/0000-0002-2273-7877
                Article
                1997
                10.1186/s13075-019-1997-5
                6790041
                31604447
                18976aec-d091-4979-ad10-bf3474f6c266
                © The Author(s). 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 April 2019
                : 5 September 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004844, National Cheng Kung University Hospital;
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Orthopedics
                polymyositis,dermatomyositis,systemic lupus erythematosus,systemic rheumatic disease,opportunistic infection

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