Abstract
Biologic disease-modifying anti-rheumatic drugs (bDMARD) have transformed the treatment paradigm of chronic autoimmune rheumatic diseases (ARDs), but they are often associated with adverse drug reactions. The present study evaluated the frequency, characteristics and type of infections, other than tuberculosis (TB), in ARD patients receiving bDMARDs. The multicentre, cross-sectional, retrospective, observational study was conducted across 12 centers in Karnataka, India, between January to August 2016. The study included patients receiving bDMARD therapy for various ARDs. Outcome variables considered were any infection, minor infections and major infections, other than TB. Clinical variables were compared between infection and no infection group, and the increase in the likelihood of infection with respect to various clinical variables was assessed. The study involved 209 subjects with a median (range) age of 41 (16–84) years and male to female ratio of 0.97:1. A total of 29 (13.88%) subjects developed infection following bDMARD therapy, out of whom a majority had minor infection (n = 26). The likelihood of developing any infection was noted to be more in subjects receiving anti-TNF (golimumab, P = 0.03) and those on three or more conventional synthetic (cs) DMARDs (P < 0.01). Infection risk was higher in patients with systemic lupus erythematosus (P = 0.04), other connective tissue disease (P < 0.01) and in patients with comorbidities (P = 0.13). The risk of infection was associated with the use of anti-TNF therapy and more than three csDMARDs, co morbidities and Adds such as systemic lupus erythematosus and connective tissue disease.
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Yamanaka H, Goto K, Suzuki M (2012) Bacterial infection in the limbs of patients with rheumatoid arthritis during biological agent therapy. Open J Rheumatol Autoimmune Dis 2:47–52
Hofmann K, Clauder A-K, Manz RA (2018) Targeting B cells and plasma cells in autoimmune diseases. Front Immunol 9:835
Boyman O, Comte D, Spertini F (2014) Adverse reactions to biologic agents and their medical management. Nat Rev Rheumatol 10:612–627
Pichler WJ (2006) Adverse side-effects to biological agents. Allergy 61:912–920
Her M, Kavanaugh A (2016) Alterations in immune function with biologic therapies for autoimmune disease. J Allergy Clin Immunol 137:19–27
Singh JA, Cameron C, Noorbaloochi S et al (2015) Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis. Lancet 386:258–265
Díaz-Lagares C, Pérez-Alvarez R, García-Hernández FJ et al (2011) Rates of, and risk factors for, severe infections in patients with systemic autoimmune diseases receiving biological agents off-label. Arthritis Res Ther 13:R112
Aletaha D, Neogi T, Silman AJ et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 69:1580–1588
Petri M, Orbai A-M, Alarcón GS et al (2012) Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677–2686
Rudwaleit M, van der Heijde D, Landewé R et al (2011) The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 70:25–31
Taylor W, Gladman D, Helliwell P et al (2006) Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 54:2665–2673
Dougados M, van der Linden S, Juhlin R et al (1991) The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum 34:1218–1227
Chopra A (2012) Epidemiology of rheumatoid arthritis. In: Mukherjee S, Ghosh A (ed) Monograph on rheumatoid arthritis. Indian College of Physicians, Academic Wing of API India, Marksman Media Service, Kolkata, pp 1–9
Doran MF, Crowson CS, Pond GR, O’Fallon WM, Gabriel SE (2002) Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum 46:2287–2293
Singh JA (2016) Infections with biologics in rheumatoid arthritis and related conditions: a scoping review of serious or hospitalized infections in observational studies. Curr Rheumatol Rep 18:61
Dixon WG, Watson K, Lunt M, Hyrich KL, Silman AJ, Symmons DPM (2006) Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 54:2368–2376
Smitten AL, Choi HK, Hochberg MC et al (2008) The risk of hospitalized infection in patients with rheumatoid arthritis. J Rheumatol 35:387–393
Quartuccio L, Zabotti A, Zotto SD, Zanier L, De Vita S, Valent F (2018) Risk of serious infection among patients receiving biologics for chronic inflammatory diseases: use-fulness of administrative data. J Adv Res. https://doi.org/10.1016/j.jare.2018.09.003
Yun H, Xie F, Delzell E et al (2016) Comparative risk of hospitalized infection associated with biologic agents in rheumatoid arthritis patients enrolled in medicare. Arthritis Rheumatol 68:56–66
Wolfe F, Michaud K, Anderson J, Urbansky K (2004) Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy. Arthritis Rheum 50:372–379
Kalb RE, Fiorentino DF, Lebwohl MG et al (2015) Risk of serious infection with biologic and systemic treatment of psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). JAMA Dermatol 151:961–969
Gerfaud-Valentin M, Jamilloux Y, Iwaz J, Sève P (2014) Adult-onset Still’s disease. Autoimmun Rev 13:708–722
Ruscitti P, Giacomelli R (2018) Pathogenesis of adult onset still’s disease: current understanding and new insights. Expert Rev Clin Immunol 14:965–976
Maria AT, Le Quellec A, Jorgensen C, Touitou I, Rivière S, Guilpain P (2014) Adult onset Still’s disease (AOSD) in the era of biologic therapies: dichotomous view for cytokine and clinical expressions. Autoimmun Rev 13:1149–1159
Peckham D, Scambler T, Savic S, McDermott MF (2017) The burgeoning field of innate immune-mediated disease and autoinflammation. J Pathol 241:123–139
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Karnataka Rheumatology Association (Association of rheumatologists).
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Authors S. Chandrashekara, Vineeta Shobha, Vijay Rao, Anu Desai, Ramesh Jois, B. G. Dharmanand, Sharath Kumar, Pradeep Kumar, Chethana Dharmapalaiah, Kurugodu Mathada Mahendranath, Shiva Prasad, Manisha Ashwin Daware, Yogesh Singh, Uma Karjigi, Nagaraj S, and K. R. Anupama declare that they have no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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Chandrashekara, S., Shobha, V., Rao, V. et al. Incidence of infection other than tuberculosis in patients with autoimmune rheumatic diseases treated with bDMARDs: a real-time clinical experience from India. Rheumatol Int 39, 497–507 (2019). https://doi.org/10.1007/s00296-019-04245-4
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DOI: https://doi.org/10.1007/s00296-019-04245-4