Eosinophils play a key role in the pathophysiology of sinonasal polyposis; their role in chronic rhinosinusitis without polyposis is less clear. To investigate this further, we biopsied diseased sinonasal tissue from 116 patients undergoing endoscopic sinus surgery and normal nasal mucosa from 24 controls. The patients were grouped, according to the nasal endoscopic appearance of their disease, into four clinical groups: chronic rhinosinusitis with no polyps, grade 1 polyps, grade 2 polyps, and grade 3 polyps. We also measured the peripheral blood eosinophil count. Histological analysis of the inflammatory cell content of the biopsies was carried out. The percentage of eosinophils in tissue from each of the clinical groups was significantly higher than that from the controls. There was no significant difference between the percentage of eosinophils in any of the clinical groups, but a trend. Peripheral eosinophil count increased with increasing severity of nasal disease.

BackgroundStrong genetic association has been reported between RA and human leukocyte antigen (HLA) regions, particularly HLA-DRB1 alleles with the shared epitope (SE). SE alleles are associated with seropositivity, erosions and higher disease activity (DA) in RA.ObjectivesTo evaluate the association between SE alleles and the presence of multiple poor prognostic factors (PPFs) of seropositive (anti-citrullinated protein antibody [ACPA] and/or RF) and erosive RA; as well as changes in DA.MethodsWe analysed patients (pts) enrolled in a large sequential RA registry established in 2003; most had established RA and annual clinical evaluations. Pts with baseline (BL) data on SE status were included. A commercially available kit (Qiagen, USA) was used for HLA genotyping. HLA-DRB1 serotypes were assessed from DNA sequences using allele-specific polymerase chain reaction methods and categorised as pts with no, 1 or 2 SE alleles. Changes from BL were compared in pts with vs without SE alleles. The association of multiple PPFs and SE status was evaluated using multinomial logistic models. The association between change in DA and SE status was analysed using linear regression models with age, sex, disease duration (DD), co-morbidities and biologic DMARDs as covariates.Abstract AB1295 – Table 1Baseline Characteristics by SE statusNo SE alleles(n=241)1 SE allele(n=275)2 SE alleles(n=173) Mean (SD) age, years57.7 (13.6)58 (13.9)57.8 (13.6)Female, n (%)202 (83.8)219 (79.6)141 (81.5)Mean (SD) RA duration, years12.9 (12.1)17 (13.3)16.1 (12.2)Biologic DMARDs, n (%)83 (34.4)145 (52.7)83 (48.0)ACPA+, n (%)118 (49.0)196 (71.3)137 (79.2)Erosions, n (%)116 (48.1)168 (61.1)114 (65.9)RF+, n (%)120 (49.8)195 (70.9)128 (74.0)Double positive, n (%)100 (41.5)174 (63.3)121 (69.9)DAS28 (CRP), mean (SD)3.8 (1.5)4.2 (1.6)4.3 (1.6)Abstract AB1295 – Table 2Multivariate Analysis of Impact of SE Status on Change in DADAS28 (CRP) modelCDAI modelSDAI model Coefficientp valueCoefficientp valueCoefficientp value 1 or 2 SE alleles (vs no SE)0.240.0312.710.0273.250.013Baseline DA–0.41<0.001–0.46<0.001–0.48<0.001Age, years0.010.2710.040.3670.040.406Female (vs male)0.110.4352.520.0992.120.198No. of co-morbidities0.110.0031.250.0031.420.002Biologic DMARD (yes vs no)0.41<0.0013.790.0024.090.001Adjusted R-square0.230.270.29ResultsOf 689 RA pts included, no, 1 and 2 SE alleles were reported in 241 (35.0%), 275 (40.0%) and 173 (25.1%) pts, respectively. At BL, pts with SE alleles (vs no SE) were more likely to have PPFs, and had longer DD and higher DA (table 1). The odds ratio (OR) for seropositive erosive RA in pts with 2 and 1 SE alleles (vs no SE) was 5.44 (95% CI 2.39, 12.39) and 2.87 (1.32, 6.23; Fig), respectively. The OR for double seropositivity in pts with 2 and 1 SE alleles (vs no SE) was 4.27 (95% CI 2.51, 7.28) and 2.56 (1.66, 3.94), respectively. A total of 551 pts had DA measures at BL and 1 year follow-up. After controlling for BL covariates, pts with SE (vs no SE) had an average increase in DAS28 (CRP) of 0.24 (p=0.031), CDAI of 2.71 (p=0.027) an...

Background:The mechanistic association ofHLA-DRB1alleles that code a “shared epitope” (SE) with rheumatoid arthritis (RA) is not yet clear. Previous data has suggested the carriage of SE is associated with the production of cyclic citrullinated peptide antibodies (anti-CCP)1and severe RA2-4. The interrelationship among SE, anti-citrullinated protein antibody (ACPA) positivity and disease outcomes is not fully understood.Objectives:To assess the RA prognosis associated with the carriage of SE, in relation to ACPA positivity.Methods:Pts enrolled in a large RA registry, Brigham and Women’s Hospital RA Sequential Study between March 2003 to June 2018, with known SE and ACPA status were included in the analysis. HLA-DRB1 SE status was determined by allele-specific polymerase chain reaction and DNA sequencing for most of the subjects and by GWAS-based imputation for the rest. Disease activity (DA) was measured at baseline (BL) and 1-year follow-up by DAS28(CRP), CDAI and SDAI. Pts were stratified by SE+ (1 or 2 SE alleles) and SE- (0 alleles) and ACPA status. We analyzed the relationship of SE with ACPA positivity and change in DA by a linear regression model separately. A mediation analysis was used to examine the mediating effect of ACPA on association between SE and change in DA.Results:Out of 926 pts included in the analysis, 65.1% were SE+, of whom 75.6% were ACPA+. In comparison, 51.7% were ACPA+ in SE- pts. SE+ pts were similar with SE- pts in age, gender, BMI and smoking status, but had longer disease duration, were more likely to be rheumatoid factor positive, have erosive disease and higher comorbidity burden irrespective of ACPA status. The differences were more pronounced if the pts were also ACPA+. Adjusting for BL differences, pts with SE 1 and 2 alleles (vs 0) had an odd ratio of 1.97 (95% CI:1.36-2.84; p=0.0003) and 3.82 (95% CI: 2.44-5.98; p<.0001) to be ACPA +, respectively. The regression analysis suggests that SE+ (vs SE-) pts had an average increase in DAS28 (CRP) of 0.22 (p=0.033), CDAI of 2.07 (p=0.045) and SDAI of 2.43 (p=0.029) over a year (Fig 1). Using a mediation analysis, the direct effect of SE+ account for 78.8% to 81.0% of total effect in the increase in DAS28 (CRP), CDAI and SDAI, and the indirect effect mediated by ACPA account for 19.0% to 21.2% (Table 1).Table 1.Mediation Analysis for SE and ACPA Association with Change in DAParameterChange in DAS28 CRP (N=666)Change in CDAI (N=653)Change in SDAI (N=629)EstimateP-valueEstimateP-valueEstimateP-valueTotal Effect of SE on DA change0.220.0342.050.0472.400.030Direct effect of SE on DA change excluding mediation of ACPA0.170.1011.570.1401.890.098Indirect effect of SE on DA change due to ACPA mediation and interaction0.040.1830.480.1330.510.143The model is adjusted with other covariates: Age, Gender, Charlson comorbidity score; baseline biologic use, Smoking status, baseline DA, Interaction term (ACPA*SE)Figure 1.Linear Regression Model for SE Association with Change in Disease Activity *Estimates, p-values are shown as data labels on the graphs; Change in disease activity (DA) = (follow-up DA- baseline DA); The above model is adjusted for age, gender, CCI, baseline DA, baseline biologic use, SE status and smoking statusConclusion:SE is strongly related to ACPA and a greater burden of disease in RA pts. In pts receiving standard treatments including biologics, SE is predictive of a greater increase in DA, which is partially mediated by the presence of ACPA.References:[1] Dayan I, et al.,Arch of Rheumatology, 2010;25:012-018.[2] Gregerson PK, et al,Arthritis Rheum. 1987;30:1205-1213.[3] Turesson C, et al.Arthritis Res Ther. 2005;7:R1386-1393.[4] Moreno I, et al.J Rheumatol. 1996;23:6-9.Disclosure of Interests:Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Joshua Bryson Shareholder of: I own shares of Bristol-Myers Squibb Company, Employee of: I am a paid employee of Bristol-Myers Squibb Company, Qian Xia Shareholder of: I own shares of Bristol-Myers Squibb Company, Employee of: I am a paid employee of Bristol-Myers Squibb Company, Niyati Sharma Consultant of: I work as a consultant for Bristol-Myers Squibb Company, Sheng Gao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sonie Lama Shareholder of: I own shares of Bristol-Myers Squibb Company., Employee of: I am a paid employee of Bristol-Myers Squibb Company., Michael E. Weinblatt Grant/research support from: BMS, Amgen, Lilly, Crescendo and Sonofi-Regeneron, Consultant of: Horizon Therapeutics, Bristol-Myers Squibb, Amgen, Abbvie, Crescendo, Lilly, Pfizer, Roche, Gilead, Nancy Shadick Grant/research support from: Mallinckrodt, BMS, Lilly, Amgen, Crescendo Biosciences, and Sanofi-Regeneron, Consultant of: BMS

Introduction: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with poor prognosis in patients with rheumatoid arthritis (RA). Previous data from randomized controlled trials and clinical practice have shown anti-CCPpositive (?) patients had a better response to treatment with abatacept or tumor necrosis factor inhibitor (TNFi) treatment than those who were anti-CCP negative. This study assessed the association between baseline anti-CCP2 [a surrogate for anti-citrullinated protein antibody (ACPA)] concentration and 6-month treatment responses to abatacept or TNFi in patients with RA.Methods: This real-world analysis included biologic-experienced patients from CERTAIN (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory CoNditions) who initiated abatacept or TNFi, had prior biologic disease-modifying drug exposure and baseline anti-CCP2 concentration/ serostatus and serum samples (baseline and 6 months). Baseline demographics and disease characteristics were compared. Change from baseline at 6 months in Clinical Disease Activity Index (CDAI) score and patient-reported outcomes [PROs: pain, fatigue, patient global assessment (PtGA), modified Health Assessment Questionnaire (mHAQ) score], by baseline anti-CCP2 quartile and binary cut-off ([ 10-250 and [ 250 U/ml), were evaluated separately in the abatacept and TNFi groups using a linear regression model adjusted for age, sex, CDAI/ PROs, comorbidity index, and methotrexate use. Results: Included were 138 abatacept and 137 TNFi initiators who were anti-CCP2?. At

Background:Rheumatoid arthritis (RA) has been shown a strong genetic association with particularHLA–DRB1alleles containing shared epitope (SE). However, whether SE is clinically useful in treatment choices is insufficiently investigated1and previous studies have presented mixed findings in the role of SE in the response of TNFi therapies2,3.Objectives:To assess the role of SE in response to TNFi treatment in real-world RA patients (pts).Methods:Pts enrolled in a large RA registry, Brigham and Women’s Hospital RA Sequential Study, with known SE and received TNFi therapies were included for the analysis. TNFi pts were identified by the first-time use of the drugs between March 2003 to June 2018. For this analysis, all pts were followed up to 1 year. Summary statistics are reported for demographics, serostatus and disease activity (DA) at baseline and follow-up, stratified by SE status. Given the strong association of SE and anti-citrullinated protein antibody (ACPA), the analysis was further stratified by ACPA status. The effect of SE on change in DA was assessed using linear regression model with age, gender, RA disease duration, baseline DA, smoking status, SE, ACPA and ACPA-SE interaction as covariates.Results:Of the 484 TNFi pts included in the study, 68.8% were SE+. SE+ pts (vs SE-) were more likely to be rheumatoid factor positive, have erosive disease and a higher disease duration, irrespective of ACPA status. No difference in the change of DA was observed by SE. In SE- pts, ACPA+ pts had a greater reduction of DA than ACPA- pts (Table 1). After accounting for baseline differences, there was no significant effect of SE status on the mean change from baseline in any of the 3 DA measures.(Figure 1) The change in DA was not associated with ACPA but was significantly affected by disease duration and baseline DA.Table 1.Disease Activity in TNFi Patients, Stratified by SE and ACPA StatusParameterSE+ (1 & 2 alleles, n=333)SE- (n=151)ACPA+ACPA–OverallACPA+ACPA-Overall(n=264)(n=69)(n=333)(n=90)(n=61)(n=151)Baseline, Mean (SD)DAS28 CRP3.94 (1.69)3.57 (1.61)3.86 (1.67)3.85 (1.49)3.45 (1.65)3.69 (1.57)CDAI23.06 (18.13)18.95 (15.96)22.25 (17.78)21.91 (15.96)17.72 (17.06)20.26 (16.48)SDAI24.08 (18.82)19.96 (16.59)23.27 (18.45)22.58 (16.34)18.55 (17.87)20.99 (17.01)Follow-up, Mean (SD)DAS28 CRP3.42 (1.55)2.69 (1.32)3.27 (1.53)3.19 (1.43)3.11 (1.53)3.16 (1.47)CDAI17.61 (15.53)12.11 (12.65)16.51 (15.14)15.15 (13.35)14.94 (14.73)15.07 (13.84)SDAI18.35 (15.73)12.45 (12.78)17.15 (15.34)15.31 (13.81)15.71 (15.45)15.46 (14.38)Change, Mean (SD)DAS28 CRP-0.48 (1.31)-0.65 (1.53)-0.52 (1.36)-0.52 (1.50)-0.24 (0.93)-0.42 (1.34)CDAI-4.29 (13.16)-4.79 (13.13)-4.39 (13.12)-6.45 (13.56)-2.63 (9.58)-4.99 (12.28)SDAI-4.74 (14.13)-5.07 (13.90)-4.80 (14.05)-6.87 (14.21)-2.97 (10.32)-5.41 (12.98)Figure 1.Linear Regression Model for Change in Disease Activity*Estimates, p-values are shown as data labels on the graphs; The above model is adjusted for age, gender, RA duration, smoking status, SE status, baseline DA, ACPA and ACPA*SE statusConclusion:This real-world study validates the finding from previous studies conducted in clinical settings that SE does not differentiate treatment response for TNFi therapies.References:[1]Saruhan-Direskeneli G, et al.Rheumatology (Oxford) 2007;46(12):1842-44[2]Skapenko A, et al.Clin Exp Rheumatol2019;37(5):783-790[3]Rigby W, et al.Annals of the Rheumatic Diseases2019;78(2):263-264Disclosure of Interests:Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Joshua Bryson Shareholder of: I own shares of Bristol-Myers Squibb Company, Employee of: I am a paid employee of Bristol-Myers Squibb Company, Qian Xia Shareholder of: I own shares of Bristol-Myers Squibb Company, Employee of: I am a paid employee of Bristol-Myers Squibb Company, Niyati Sharma Consultant of: I work as a consultant for Bristol-Myers Squibb Company, Chidananda Samal Consultant of: I work as a consultant for Bristol-Myers Squibb Company, Sonie Lama Shareholder of: I own shares of Bristol-Myers Squibb Company., Employee of: I am a paid employee of Bristol-Myers Squibb Company., Michael E. Weinblatt Grant/research support from: BMS, Amgen, Lilly, Crescendo and Sonofi-Regeneron, Consultant of: Horizon Therapeutics, Bristol-Myers Squibb, Amgen, Abbvie, Crescendo, Lilly, Pfizer, Roche, Gilead, Nancy Shadick Grant/research support from: Mallinckrodt, BMS, Lilly, Amgen, Crescendo Biosciences, and Sanofi-Regeneron, Consultant of: BMS