POS0709 THE RISK OF SERIOUS INFECTIONS IN PATIENTS WITH EARLY INFLAMMATORY ARTHRITIS: RESULTS FROM A LARGE UK COHORT (NEIAA)
Authors: M. A. Adas, K. Bechman, B. Zuckerman, M. Russell, S. Patel, D. Nagra, I. Karafotias, M. Gibson, S. Gallagher, E. Price, M. Garton, A. Rutherford, A. Cope, S. Norton, J. Galloway
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> There is little evidence available that specifically assesses morbidity and mortality in early RA. Most evidence is derived from people with well-established disease and a substantial burden of comorbidities <sup>[*]</sup>. <h3>Objectives:</h3> To identify the risk of serious infections (SI) admissions and SI mortality according to the initial treatment strategy, using conventional synthetic disease modifying anti-rheumatic drugs (csDMARD) and corticosteroids, in patients recruited to the National Early Inflammatory Arthritis Audit (NEIAA). <h3>Methods:</h3> An observational cohort study design was used. The population included adults in England with a new onset RA, fulfilling ACR/EULAR 2010 criteria, between April 2018-April 2021. Outcomes studied were SIs, defined by infections requiring hospitalisation (primary admission diagnosis/nosocomial acquisition) or death (SI stated on death certificate), identified using NHS Digital linkage. Patients characteristics were tabulated by treatment strategies. Hazard ratios (HR) were calculated using single failure Cox proportional-hazards models, with confounders-adjusted models (age, gender, smoking status, comorbidities, social deprivation) and fully-adjusted models including disease factors (seropositivity, DAS28). Individuals were considered at risk from the date of RA diagnosis, and censored at SI event, death, or April 2021 (whichever was earliest). <h3>Results:</h3> Initial DMARD therapy was known for 9,591 patients, of whom 5,887 were on methotrexate/MTX based strategies (mono or combo), 2,457 on csDMARD strategies other than MTX (of which 1,375 on combo and 1,082 on mono non-MTX strategies) and 1,247 on no DMARD strategy. 7,501 patients were on corticosteroids at baseline. Mean age 59.3 years (+/-15); 63% female; smoking status (20% current; 30% ex-smokers); comorbidities (21% hypertension; 9% diabetes; and 11% lung disease). Rheumatoid Factor/CCP antibodies were positive in 68%. At presentation, median diseases scores were 5.0 (interquartile range (IQR): 4.0-5.9) for DAS28, 1.1 (IQR: 0.6-1.6) for health assessment questionnaire (HAQ) and 24 (IQR: 16.0-33.0) for musculoskeletal health questionnaire (MSKHQ) where higher score indicate butter MSK health. In our cohort there were 523 SI admissions with 158.74 patients years of follow up, and 18 SI deaths with 159.40 years of follow up. Corresponding to an incidence rates per 100 person-years for SI admissions: 3.29 [95% CI: 3.02-3.58] and SI deaths: 0.11 [95% CI: 0.07-0.17]. In fully-adjusted models, increasing age predicted both SI admissions and deaths. Being a current smoker, having a comorbidity, higher disease activity (DAS28), symptom burden (MSKHQ) and disability (HAQ) at presentation associated with more SI admissions. For each 1 unit increase in DAS28, the risk of SI admissions increased by 8% (HR 1.09 [95% CI:1.02-1.17]). Seropositivity did not associate with SI. MTX-based strategies (0.76 [95% CI:0.63-0.91]) and csDMARD combination therapy (0.72 [95% CI:0.55-0.95]) associated with fewer SI admissions compared to no DMARD. Mono non-MTX strategies were not correlated with SI admissions. In unadjusted models, corticosteroid associated with more SI admissions (1.28 [95% CI:1.02 -1.61]); however, in fully-adjusted models this relation was no longer statistically significant (1.08 [95% CI: 0.83-1.39]). All csDMARD strategies were not associated with SI deaths in any of the models. <h3>Conclusion:</h3> Patient and disease factors at diagnosis appear to be important predictors of admissions and mortality for serious infections in early RA. Infection risk appears to be greatest in those with higher RA disease activity. An important limitation is that NEIAA does not capture data on treatment changes over time and steroids use beyond baseline. <h3>REFERENCES:</h3> [1] Black RJ, Lester S, Tieu J, Sinnathurai P, Barrett C, Buchbinder R, Lassere M, March L, Proudman SM, Hill CL. Mortality estimates and excess mortality in rheumatoid arthritis. Rheumatology. 2023 Mar 15:kead106. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Maryam A. Adas: None declared, Katie Bechman: None declared, Benjamin Zuckerman: None declared, Mark Russell Has received honoraria from Lilly, Galapagos, Biogen and Menarini, and support for attending meetings from Lilly, Pfizer, Janssen and UCB., Samir Patel: None declared, Deepak Nagra: None declared, Ioasaf Karafotias: None declared, Mark Gibson: None declared, Sarah Gallagher: None declared, Elizabeth Price: None declared, Mark Garton: None declared, Andrew Rutherford: None declared, Andrew Cope: None declared, Sam Norton: None declared, James Galloway Has received honoraria from AbbVie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB.