POS0961 ASSOCIATION BETWEEN AIR POLLUTANTS AND INITIATION OF BIOLOGICAL THERAPY IN PATIENTS WITH ANKYLOSING SPONDYLITIS: A NATIONWIDE, POPULATION-BASED CASE-CONTROL STUDY

Abstract

BackgroundAnkylosing spondylitis (AS) is a systemic inflammatory disease and the first-line pharmacological therapy includes non-steroidal anti-inflammatory drugs (NSAIDs) for spinal and peripheral joint involvement and immunosuppressants including methotrexate (MTX) and sulfasalazine (SSZ) for peripheral arthritis[1]. Biological therapy under National Health Insurance (NHI) reimbursement is indicated for AS patients without adequate response to first-line therapy in Taiwan. Initiation of biologics such as tumor necrosis factor inhibitors and interleukin-17 inhibitors may act as a proxy for high disease activity. Outdoor air pollution has been found to trigger a systemic inflammatory response[2]. Therefore, we hypothesized that air pollutants may be associated with biologics use in AS patients.ObjectivesTo investigate the association between air pollutants and initiation of NHI-reimbursed biologics indicated for high disease activity in patients with AS.MethodsWe conducted a nationwide case-control study using the Taiwan National Health Insurance Research Database, and incidental AS patients from 2003 to 2013 were identified. We excluded those with visits with a diagnosis of rheumatoid arthritis, those treated with biologics including etanercept, adalimumab, and golimumab before the first date of visit with AS diagnosis, and those without outpatient visits after 2009. We identified all AS patients initiating biologics for active AS as biologics cases, and non-biologics controls for those who didn’t. Index date was designated as the date of initiation of first biologics for cases and the date of first outpatient department visits each year for controls. We matched both groups at a 1:4 ratio for gender, age at first biologic initiation (± 3 years), year of first AS diagnosis, and disease duration (± 0.3 year), and finally included 584 biologics cases and 2336 matched controls. With aid of a spatio-temporal model built by a deep-learning approach, we used the hourly concentrations of ambient air pollutants from 60 air quality censoring stations to estimate the mean exposed levels of air pollutants, including PM2.5, PM10, NO2, CO, SO2, and O3, at 374 residential locations in Taiwan within one year before index date. We examined the association of biologics initiation and air pollutants using conditional logistic regression analyses shown as adjusted odds ratio (aOR) with 95% confidence intervals (CIs) adjusting for potential confounders within one year before index date including disease duration, urbanisation level, monthly income, Charlson comorbidity index (CCI), extra-articular manifestations (i.e., uveitis, psoriasis, and inflammatory bowel disease), and use of medications for AS.ResultsThe initiation of NHI-reimbursed biologics was associated with disease duration (aOR, 8.97; 95% CI, 5.99–13.46), CCI (aOR, 1.31; 95% CI, 1.12–1.53), psoriasis (aOR, 25.06; 95% CI, 9.47–66.35), use of NSAIDs (aOR, 23.66; 95% CI, 8.96–62.46), MTX (aOR, 4.53; 95% CI, 2.93–7.00) and SSZ (aOR, 12.15; 95% CI, 8.98–15.45), prednisolone equivalent dose (mg/day) (aOR, 1.11; 95% CI, 1.05-1.18). After adjusting for potential confounders, it was associated with exposure to CO (per 1 ppm) (aOR, 8.58; 95% CI, 2.02–36.35), and NO2 (per 10 ppb) (aOR, 0.23; 95% CI, 0.11–0.50).ConclusionUse of NHI-reimbursed biologics, a proxy for high disease activity, in AS patients was positively associated with CO level, but negatively associated with NO2 level. Further studies are warranted to confirm our findings and elucidate the mechanisms.