AB0780 Prolonged proton pump inhibitor exposure is associated with development of calcinosis in systemic sclerosis
Authors: L.V. Host, C. Campochiaro, S.I. Nihtyanova, V.H. Ong, C.P. Denton
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Long-term use of proton pump inhibitors (PPI) has been associated with some safety concerns, including potential vascular calcification. In a previous retrospective analysis, we noted a possible association between PPI use and calcinosis in scleroderma (SSc). <h3>Objectives</h3> To investigate the association between PPI use and the presence and extent of calcinosis in SSc patients. <h3>Methods</h3> Data from prospectively recruited patients were collected by patient survey, physician assessment and medical records. Calcinosis was graded; size (+=&lt;1 cm, ++=≥1≤3 cm, +++=&gt;3 cm) and number of sites involved (NSI) (I=1 body site, II=2–3, III≥3). A total daily PPI equivalent dose (TDED) was calculated for each patient. We calculated PPI exposure score (PPE) by multiplying the total duration of use by TDED. For analysis, PPE was categorised into four groups; 0=no exposure, 1=up to 5 years, 2=6–10 years, 3≥10 years. Fisher's exact test was used to assess categorical variables. Logistic regression assessed association between calcinosis and independent variables. <h3>Results</h3> 216 patients were recruited, 81.5% females, mean age 57.46 (SD 13.5) years. 56.5% had limited, 31.5% diffuse SSc, 9.7% had overlap features and 2.3% other CTD. Mean disease duration was 10 years (SD 9). ANA subtypes were defined: ACA positive (31.5%), ATA (25.5%), ARA (12.0%), ANA +ENA- (11.6%), U3RNP (5.1%), ANA- (4.2%), PmSCL (3.7%) and 6.5% other antibodies. Gastroesophageal reflux symptoms occurred in 83.3% of patients, most were on PPI (81%) and 14.8% had previously been on PPI. Current calcinosis (CC) was present in 30.1% patients, 9.7% reported past calcinosis. 39.8% had calcinosis at any time (CAT). 60.2% of patients never had calcinosis. Of those with CC, 47.7% had &gt;1 site involved. The most frequent sites affected were; finger (70.8%), elbow (35.4%) and knee (18.5%). Univariable analysis found an association between disease duration and calcinosis, with odds of CAT increased by 7% per year (OR 1.07, CI 1.04–1.11, p&lt;0.001). Similarly, every year of PPE increased odds of CAT by 3% (OR 1.03, CI 1.01–1.05, p=0.003). Increasing age associated with CAT (odds increasing by 2% per annum, p=0.043). Exposure to a standard dose of PPI for over 10 years increased the odds of calcinosis by 4 times (OR 4.07, CI 1.68–9.85, p=0.002) compared to no exposure. PPE category associated with NSI (p=0.04). 73.3% of patients with large volume calcinosis (&gt;3 cm) had a PPE for &gt;10 years and all with calcinosis &gt;3 cm had exposure to PPI. Multivariable logistic regression found that disease duration (OR 1.07, CI 1.03–1.11, p=0.001) and antibody specificity strongly associated with calcinosis. Presence of ATA (OR 0.32, CI 0.14–0.75 p=0.008), ANA- (OR 0.13, CI 0.02–0.79, p=0.026), and ANA +ENA- (OR 0.17, CI 0.05–0.52, p=0.002) reduced odds of calcinosis. Although the effect of PPIs on calcinosis was attenuated after adjusting for disease duration and antibodies, higher exposure to PPIs remained a significant predictor of calcinosis, with PPE category (&gt;10) increasing risk of CAT (OR 3.34, CI 1.16–9.17, p=0.025). <h3>Conclusions</h3> Our data support a novel association of PPI exposure with calcinosis and confirm association of disease duration and antibody profile. Given the clinical impact of calcinosis, a potentially modifiable risk factor of PPI exposure warrants further study. <h3>Disclosure of Interest</h3> L. Host Grant/research support from: Supported jointly by an educational research grant by the Australian Rheumatology Association, Roche and ARA WA, C. Campochiaro: None declared, S. Nihtyanova: None declared, V. Ong: None declared, C. Denton Consultant for: Consulted for Roche/Genentech, Actelion, GlaxoSmithKline, Sanofi-Aventis, Inventiva, Boehringer-Ingelheim, CSL Behring, EMD Serono, and UCB Pharma