X. Mariette

Fcγ receptor type IIIA polymorphism influences treatment outcomes in patients with rheumatoid arthritis treated with rituximab

Objective To assess the association between a single nucleotide polymorphism in the gene of FCGR3A and the response to treatment with rituximab (RTX) in rheumatoid arthritis (RA). Methods SMART is a randomised open trial assessing two strategies of re-treatment in patients responding to 1 g infusion of RTX with methotrexate on days 1 and 15 after failure, intolerance or contraindication to tumour necrosis factor (TNF) blockers. Among the 224 patients included, 111 could be genotyped and were included in an ancillary study of SMART. Univariate and multivariate analyses adjusted on disease activity score on 28 joints were performed to assess whether FCGR3A-158V/F polymorphism was associated with European League Against Rheumatism response at week 24. Results Among the 111 patients, 90 (81%) were responders of whom 30 (27%) were good responders. V allele carriage was significantly associated with a higher response rate (91% of responders vs 70%, OR 4.6 (95% CI 1.5 to 13.6), p=0.006). These results were also confirmed in rheumatoid factor-positive patients (93% vs 74%, p=0.025). In multivariate analysis, V allele carriage was independently associated with response to RTX (OR 3.8 (95% CI 1.2 to 11.7), p=0.023). Conclusion The 158V/F polymorphism of FCGR3A seems to influence the response to RTX in patients with RA after failure, intolerance or contraindication to TNF blockers.

Association between -871C>T promoter polymorphism in the B-cell activating factor gene and the response to rituximab in rheumatoid arthritis patients.

OBJECTIVEnTo determine whether a functional single-nucleotide polymorphism in the B-cell activating factor (BAFF) gene correlates with the response to treatment with rituximab (RTX) in RA.nnnMETHODSnSMART is a randomized open trial (NCT01126541) assessing two strategies of re-treatment in patients responding to 1-g infusion of RTX with MTX on days 1 and 15 after failure, intolerance or contraindication to TNF blockers. Among the 224 patients included, 115 provided informed consent, could be genotyped and were included in an ancillary study of SMART assessing European League Against Rheumatism (EULAR) response rate after the first course of RTX according to BAFF-871C>T polymorphism. Baseline clinical factors (patients and disease characteristics) and biologic factors (ESR, CRP, RF, anti-citrullinated peptide antibodies, serum immunoglobulins) were collected. Univariate analyses were performed to assess whether BAFF-871C>T polymorphism was associated with EULAR response at week 24. Results with P < 0.15 obtained in univariate analyses were then included in multivariate analysis adjusted on DAS28 level.nnnRESULTSnNinety-three patients (81%) were responders, of whom 31 (27%) were good responders. CC genotype was significantly associated with a higher response rate [92% of responders vs 64% for TT genotype, odds ratio (OR) = 6.9; 95% CI 1.6, 29.6; P = 0.03]. These results were also confirmed in RF-positive patients (96% vs 58%, P = 0.006). In multivariate analysis, C allele carriage was independently associated with response to RTX (OR = 4.1; 95% CI 1.3, 12.7; P = 0.017).nnnCONCLUSIONnThe BAFF-871C>T polymorphism seems to influence the response to RTX in RA patients after failure or intolerance to TNF blockers.

OP0035 Tolerance of Rituximab, Abatacept and Tocilizumab in Common Practice: Analysis of the 3 Registries of the French Society of Rheumatology (Air, Ora and Regate)

Objectives To perform a joint analysis of the safety of abatacept (ABA), rituximab (RTX) and tocilizumab (TCZ) in real life. Methods The AIR, ORA and REGATE French Society of Rheumatology registries follow up prospectively patients with rheumatoid arthritis treated with RTX, ABA or TCZ. The analyses took into account serious infections that occurred in the 12 months that followed an infusion of rituximab in the absence of initiation of a new biologic or those who occurred under abatacept or tocilizumab or in the 3 months that followed their discontinuation, in the absence of initiation of a new biologic. Serious infections and cancers were validated by the review of the charts of patients. Results 1980 patients treated with RTX (current follow up of 6844 patient-years), 1024 patients with ABA (2882 patient-years), and 1503 patients with TCZ (1552 patient-years) (database of January 2013 for RTX and ABA and August 2013 for TCZ). – Serious infections: 309 serious infections occurred under RTX (4.5 serious infections/100 patient/years). 102 serious infections occurred under ABA (3.5 serious infections/100 patient/years). 55 serious infections occurred under TCZ (5.2 serious infections/100 patient/years). 3 tuberculosis infections (0.04/100 patient/years) occurred under RTX, 2 (0.07/100 patient/years) under ABA and no tuberculosis under TCZ. – Cancers: 85 cancers occurred under RTX (1.2/100 patient-years) including 14 non-melanoma skin cancers (0.2/100 patient/years), 71 solid cancers and haematological malignancies (1.0/100 patient/years) including 8 haematological malignancies (0.1/100/patient/years with 1 lymphoma).40 cancers occurred under ABA (1.4/100 patient/years) including 13 non-melanoma skin cancers (0.5/100 patient/years), 27 solid cancers and hematological malignancies (0.9/100 patients/year) including 4 haematological malignancies (0.14/100 patient/years, without lymphoma). 10 cancers were observed under TCZ (1.0/100 patient/years) including 2 non melanoma skin cancers (0.19/100/patient/years) 8 solid cancers and haematological malignancies 0.8/100 patient/years) including 3 haematological malignancies (0.29/100 patient/years) with 3 lymphomas. Conclusions Incidences of serious adverse events in real life patients with comorbidities were similar under ABA, RTX and TCZ to what is expected in rheumatoid arthritis treated with anti-TNF. With ABA, RTX and TCZ, the incidence of tuberculosis is low. Adjusted statistical comparisons of safety, efficacy and drug retention rate of these 3 biologics are currently performed. Disclosure of Interest None declared

THU0173 Retention Rates of Adalimumab, Etanercept and Infliximab as First and Second-Line Biologic Therapy in Patients with Rheumatoid Arthritis in Daily Practice: The Maintain Study

Background Efficacy and safety of TNFα inhibitors (TNFi) in rheumatoid arthritis (RA) have been evaluated in randomized controlled trials. The analysis of observational studies and registries provides additional real-world information. Drug survival rate reflects the real world balance between efficacy and safety. Objectives The primary objective of this study was to compare the retention rates (RR) of adalimumab (ADA), etanercept (ETN) and infliximab (IFX) as 1st-line biologic therapy in RA. The secondary objectives were to determine causes of discontinuation, factors associated with a better retention, and RR of 2d-line TNFi. Methods This is a retrolective, multicentre study in 8 French Rheumatology centres. The medical charts of all pts with RA who started TNFi therapy between March 1st 2005 and April 30th 2009 were reviewed, based on diagnosis and treatment (TT) codes, with a follow-up duration of min. 2 to max. 6 yrs. The RR was estimated using the Kaplan-Meier method. TNFi were compared after adjusting the inverse of a propensity score, using a Cox model. Factors associated with a better RR were identified by multivariate analysis. Results 706 pts were included in the study. The first TNFi was ADA in 203 (28.8%), ETN in 404 pts(57.2%) and IFX in 99 pts (14%). The percentage of pts still on TT after 2 yrs was 54.9%, 61.9% and 48.7% for ADA, ETN and IFX respectively. The median duration of trt was 31 mths for ADA (95% CI [19-38]), 45 mths for ETN (95% CI [35-51]) and 23 mths for IFX (95% CI [16-36]). The Hazard ratios (HRs) for discontinuing the first TNFi were significantly greater with ADA and IFX than with ETN (1.315, 95% CI [1.050-1.648] and 1.380, 95% CI [1.041-1.828] respectively). There was no significant difference between the 2 monoclonal antibodies. The HR for TT discontinuation due to lack of efficacy was significantly higher with ADA than ETN (1.511, 95% CI [1.152-1.982]). The HR for stopping trt due to adverse events was significantly higher with IFX than ETN (2.175 (95% CI [1.402-3.374]). Baseline characteristics associated with a better retention of the first TNFi were a higher number of previous DMARDs and a higher ESR. A second TNFi was administered to 231 pts: ADA in 105, ETN in 106, and IFX in 20 pts. The median retention period was 11 mths for ADA (95% CI [7-17]), 43 mths for ETN (95% CI [19.1-58]), and 19.1 mths for IFX (95% CI [5-NE]). The HR for discontinuing ADA was significantly greater than for ETN (2.023, 95% CI [1.393-2.937]). The HRs for stopping due to lack of efficacy or adverse events (AE) were significantly greater for ADA than for ETN (1.998, 95% CI [1.321-3.024] and 2.188, 95% CI [1.017-4.708] respectively). Conclusions ETN had a better RR as a first-line biotherapy in RA, with a HR for discontinuing ADA or IFX that was about 30% greater than that of ETN. As first-line biologic therapy, ETN had fewer withdrawals for inefficacy than ADA, and fewer withdrawals for AE than IFX. As a 2d-line TNFi, ETN also had a better RR than ADA. Disclosure of Interest A. Frazier-Mironer Consultant for: Pfizer, A. Cantagrel Grant/research support from: Chugai, Pfizer, UCB, Consultant for: Laboratoires BMS, Chugai, MSD France, Novartis, Pfizer, Roche, UCB, Speakers bureau: Laboratoires Abbott, BMS, Chugai, MSD France, Nordic-Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB, B. Combe Grant/research support from: Pfizer, Roche, Chugai, Consultant for: BMS, Celgene, Merck, Novartis, Pfizer, Roche, Chugai, UCB, Speakers bureau: Merck, Pfizer, UCB, V. Deschamps Employee of: PFIZER, M. Dougados Grant/research support from: Pfizer, Abbott, Roche, BMS, Merck, Lilly, Novartis, Consultant for: Pfizer, Abbott, Roche, BMS, Merck, Lilly, Novartis, R.-M. Flipo Grant/research support from: Pfizer, Roche, Chugaï, Consultant for: Abbott, Astra-Zeneca, BMS, Ipsen-Ménarini, MSD, Pfizer, Roche, Chugaï, UCB, Janssen-Cilag, Paid instructor for: Abbott, Astra-Zeneca, BMS, Expansciences, Ipsen-Ménarini, MSD, Nordic-Pharma, Pfizer, Roche, Chugaï, Genzyme, UCB, I. Logeart Employee of: Pfizer, X. Mariette Consultant for: BMS, Pfizer, Roche et UCB, T. Schaeverbeke Consultant for: Roche, Chugai, Pfizer, J. Sibilia Grant/research support from: Roche, Pfizer, Merck Sharp, Bristol Myers Squibb, Speakers bureau: Roche, Chugai, Bristol Myers Squibb, Abbott, UCB, GSK, LFB, Actelion, Pfizer, Merck Sharp, Novartis, X. Le Loët Consultant for: MSD, Pfizer, Roche

OP0113 Modification of Salivary Gland Lymphocyte Pattern after Belimumab in Primary Sjogren’s Syndrome: Results of the Beliss Study

Background The BAFF (or BLyS) cytokine plays a key role in pathogenesis of primary Sjogren’s syndrome (pSS). The level of BAFF is increased in the serum and BAFF may be expressed by salivary epithelial cells and the lymphoid infiltrate of salivary glands. Moreover, BAFF is induced by innate immunity stimulation, the later playing a role in pSS pathogenesis. Belimumab, the first biological treatment inhibiting soluble BAFF/BLyS has proved its effectiveness in systemic lupus and has been recently approved for this indication. Lupus and pSS share a lot of pathogenic mechanism including interferon signature and BAFF involvement. Thus we run the first open label study of belimumab in pSS patients and recently showed that 19/30 patients (63%) achieved the primary end-point which was a composite clinico-biological outcome. Objectives To address the change in labial salivary gland (LSG) inflammation after Belimumab therapy Methods Patients were included in 2 parallel and identical studies in 2 European Centres. Patients had to fulfill AECG criteria, to be anti-SSA/SSB positive and had to have at the time of inclusion either systemic complications or early disease (<5 yrs of symptoms), or the presence of biomarker of B-cell activation. The patients were treated with belimumab 10 mg/kg W0, W2, W4 and then every four weeks until W24. Minor labial salivary gland (LSG) biopsies of the 15 patients (all female, mean age=50 yrs, mean disease duration= 5 yrs) from the French center, performed at W0 and W28, were analyzed for estimating the focus score, the B-cell/T-cell ratio (CD20 and CD3 staining), BAFF expression (BAFF (Buffy-2) staining) and NK infiltrate (NKp46 staining). Results Before treatment, significant lymphocytic sialadenitis (focus score >1) was observed in 11 (78.6%) patients before treatment, five of whom became negative (focus score <1) at w28[51] (p=0.07). The median focus score decreased from 1.6 to 0.5 (p=0.39) and the median Chisholm score from 4 to 2 (p=0.01). B-cell /T cell ratio decreased after treatment in 5 patients and remained stable in all other patients (median ratio decreased from 0.58 to 0.50, p=0.055). Before treatment, a BAFF staining was detected in 11/14 (78.6%) patients, and in only 7/14 (50.0%) after belimumab (p=0.07). The median percentage of BAFF positive cells in foci significantly decreased from 27.5% to 5% after belimumab therapy (p=0.03). NKp46 staining revealed that NK cells infiltrate was predominantly located in interstitium rather than in foci (median number of NK cell: 24.7 vs. 8.2/mm², p=0.0003), and did not change after belimumab. Conclusions There was a clear tendency in favour of a decrease in foci number, B cells and BAFF-expressing cells within LSG after belimumab therapy. It is tempting to interpret the decrease in BAFF staining as an effect of the drug on membrane BAFF-expressing cells, but it could be also only due to the decrease in B cells expressing BAFF receptors linked to soluble BAFF passively stained by the anti-BAFF antibody. After belimumab therapy, we observed regression of lymphocytic infiltration of LSG in one third of the patients. Also the percentage of BAFF positive cells significantly decreased with a trend to a decrease of B-cell/T-cell ratio. Disclosure of Interest None Declared

OP0280 Step-Down Strategy of Spacing TNF-Blockers Injections for Established Rheumatoid Arthritis in Remission: A Cost-Utility Analysis Based on the Strass Trial

Background Once remission is achieved for patients with rheumatoid arthritis (RA), treatment down-titration should be attempted, for safety issues or economic reasons. One of the proposed strategies, recently tested in the STRASS trial [1], is to progressively space injections of TNF-blockers. Objectives To assess the Incremental Cost-Effectiveness Ratio (ICER) of a strategy of progressive spacing of TNF-blocker injections (S-arm) over another maintaining them at full-dose (M-arm) in RA patients in stable remission. Methods The study was a French multi-centre 18-month equivalence randomized open-label controlled trial. It included patients receiving etanercept (ETA) or adalimumab (ADA) at stable dose for ≥1 year; in remission on 28-joint Disease Activity Score (DAS28) for ≥6 months; and with stable joint damage. In the S-arm, the interval between 2 subcutaneous injections was increased every 3 months by 50% in 4 steps, to a complete stop at step 4. If remission was not maintained, spacing was suspended or reversed to the previous interval. Costs engaged within the study-period, measured in euros, were assessed using a health insurance payer perspective encompassing medical costs (drugs, consultations and medical tests, use of emergency room and hospitalizations) and costs relative to sick leave. Utilities values used to compute Quality Adjusted Life Years (QALYs) were derived from the EQ-5D, using values validated in the French population, assessed at baseline and every 6 months. The ICER was estimated. A probabilistic sensitivity analysis was performed by computing 5000 ICERs (bootstrap). The probability of cost-effectiveness (p of CE) of the maintenance strategy was computed for different Willingness to Pay (WTP) thresholds. Results Analyses were performed on 44 patients in the S-arm and 54 in the M-arm with complete data. In the S-arm, TNF-blockers were stopped for 34.1% of the patients, tapered for 43.2%, maintained at full-dose for 18.2%. After 18 months of follow-up, 62.3% and 45.9% of the patients of the S and M-arm respectively, found their symptomatic state acceptable (p=0.08). Patients in the S-arm gained 1.106 QALYs while it was 1.264 in the M-arm (mean differences in QALYs of -0.158). After 18 months, total mean cost was 12452 euros in the S-arm and 20892 euros in the M-arm (mean cost difference of -8440 euros). The cost of TNF-blockers represented 81.0% and 92.8% of the total cost in the S and M-arms respectively. The estimated ICER was 53417 euros per QALY. The p of CE of the maintenance strategy was 0.02, 0.06, 0.22 and 0.41 for WTP thresholds fixed at 25000, 30000, 40000 and 50000 euros respectively. Conclusions Although 62.3% of the patients found their symptomatic state acceptable, the spacing strategy was found to be less effective based on QALY measures. But, it was also found to be less costly. Thus, the maintenance strategy was assessed as the strategy with the lowest probability of being cost-effective for WTP thresholds ranging from 25000 to 50000 euros. References Fautrel et al, EULAR 2013 and ACR 2013 Disclosure of Interest None declared

THU0151 Effects of Tnfα-Blockers Tapering on Occurrence of Patient-Perceived Flares in Rheumatoid Arthritis: A Subanalysis of Strass

Background Flares in rheumatoid arthritis (RA) are a patient-perceived sign of disease activity which might be particularly important to assess in the context of treatment tapering. However assessment of flares in not yet well-defined. Objectives To explore the frequency of patient perceived flares during treatment tapering in RA, and to assess agreement between patient-perceived flares and other criteria including patient-reported outcomes and change in DAS28. Methods The STRASS study was a step-down randomized trial (ref). Patients had RA, were treated with adalimumab (ADA) or etanercept (ETN), and were in DAS 28-remission (DAS ≤2.6) for ≥6 months. Patients were randomized to either the “spacing”(S) arm (where the TNF blocker was tapered gradually) or “maintaining”(M) arm, over 18 months. Flares were evaluated through a patient-reported questionnaire every 3 months, asking: “Concerning the last 3 months, did you experience symptoms of a relapse of RA?”, with subquestions on pain and swollen joints. The frequency of visits where patients reported flares was compared in the M and S arms by Wilcoxon test. Disease characteristics were compared (t-test or Wilcoxon as appropriate) between visits with vs without a flare reported for both patient and physician reported outcomes. Agreement between patient-perceived-flares and DAS28 defined relapse (DAS 28>2.6 and an increase in DAS28 of at least 0.6 points at the same visit) was assessed by kappa. Results 137 patients were included in STRASS, 64 and 73 in the S and M arms respectively: age (mean ± SD) 55±11 yrs, females 78%, RA duration 9±8 years (ref). Over the 18 months of the study, the mean number of visits where the patient reported at least one flare (out of a possible total number of visits of 6 visits), was 1.87±1.74, with 2.44±1.68 visits with flares in the S arm, and 1.37±1.65 visits with flares in the M arm (p=0.0001). For the 256 visits with patient-perceived flares, the most frequent symptom (on subquestions) was pain (91.0%), rather than swollen joints (56.6%). Comparison between visits at which patients reported flares, and visits at which patients did not, showed statistically significant differences concerning all other outcomes (table). Agreement between patient-perceived flares and DAS 28-relapse was moderate: kappa was 0.40 to 0.49 [0.22-0.65] across visits. Conclusions Patient-perceived flares discriminated well between the treatment arms in the STRASS study, and were related to worsenings in other usual outcomes in RA, indicating flares may be a useful study endpoint in tapering trials. However, agreement with DAS worsening was only moderate. Although flares are an important concept for patients with RA, more work is needed on the concept of flares. References Fautrel et al, EULAR 2013, OP0066. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.2729

FRI0155 Fifty Percent of Patients Who Tapered TNF-Blockers while in Stable Remission Are Able To Maintain A Tapered Regimen at 3 Year: Long Term Follow-Up Extension of The Strass Trial

Background Step-down strategy of spacing anti-tumor necrosis factor (TNF) agents in patients with rheumatoid arthritis (RA) in remission are feasible in the context of randomized clinical trials (RCTs). However, we lack information on the long-term sustainability of a DAS driven step down strategy in clinical practice. Objectives This long-term extension study of a tapering RCT (STRASS trial (1)) aimed to assess the rate of patients who maintained the tapered regimen of etanercept (ETA) or adalimumab (ADA) in the in S-arm (progressive injection spacing) and M-arm (full regimen) and to evaluate the rate of treatment switch for inefficacy during the 3 years following the trial. Methods This observational 36 months follow-up considered all patients who completed the STRASS RCT (1). During the follow-up, the physicians were completely free of therapeutic decision making. Physicians were contacted between April and October 2015 and the data on the 36-month period after the end of trial retrospectively collected. The co-primary outcomes were the rate of patients who were taking their initial biologic at tapered regimen and the switch rate for loss of efficacy or safety. Percentage of full regimen anti-TNF intake was calculated over the 3 first years after trial end in both arms, using data from 12-monthly follow-up time points. Results 96 patients (70.1% of patients completing the RCT) had follow-up data available up to 3 years. At the end of the STRASS RCT (Table), 72 (75%) were in LDA or remission: 47 (48.9%) were taking ETA, 35 (36.5%), ADA, 2 (2.1%) another biologic and 12 (12.5%) no biologic because of remission. In addition, amongst patients still on their initial TNF blockers, 59/80 (74%) were treated at full regimen, 21/80 (26%) at tapered regimen. 3 years later, 65/96 (67.7%) were still on their initial anti-TNF: 73.1% vs 61.4% respectively in M and S-arm, p=0.23), either at full regimen 36/96 (38%), tapered regimen 29/96 (30%, 32% vs 29%, p=0.75), or completely stopped (11.5%: 5.8% vs 18.2%, p=0.06). 28 patients (29.2%, 25% vs 34.1%, p=0.33) had switched for another biologic. The mean percentage of full regimen of antiTNF over 3 years was 70.1±30.4%: respectively 74.3±28.2% vs 64.6±32.9% (p=0.19). DAS28-VS was not different between M and S-arm (2.42 vs 2.01 (p=0.23)).Table 1. Disease activity and treatment strategy Initial M-arm Initial S-arm (n=52) (n=44) RCT end LDA or remission, n (%) 42 (80.8) 30 (68.2) Treatment spaced or no biologic, n (%) 0 (0) 33 (75.0) At 3 years LDA or remission, n (%) 31 (72.1) 27 (73.0) Full dose of initial antiTNF, n (%) 23 (44) 13 (30) Spacing initial antiTNF without stop, n (%) 15 (29) 14 (32) No biologic, n (%) 3 (6) 8 (18) Switch rate over 3 years due to relapse, n (%) 12 (32) 10 (20) Conclusions Maintenance of anti-TNF was high (68% at 3 years) in this cohort of patients with established RA treated according to the treat-to-target paradigm, with no difference between the 2 initial RCT arms. More than 1/3 of patients were received tapered anti-TNF regimen. References Fautrel B, ARD 2016;75(1):59–67 Disclosure of Interest None declared

OP0237 Polymorphisms of Gene Implicated in Type 1 Interferon Pathway Are Associated with The Clinical Response of Rituximab at 24 Weeks in Rheumatoid Arthritis

Background Rheumatoid arthritis (RA) treatment may target B-cells using rituximab (RTX), a chimeric monoclonal antibody directed against the B-cell marker CD20. Transcriptome of PBMCs from RA patients before RTX has suggested that responders differs from non-responders on the expression of genes regulated by type 1 interferon (IFN) (1) suggesting a possible contribution of type 1 IFN pathway genes such as interferon regulatory factor 5 (IRF5), tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 4 (STAT4), osteopontin (SPP1) and interferon regulatory factor 7 (IRF7). Objectives To study 8 IRF5, TYK2, STAT4, SPP1 and IRF7 variants as candidate predictors of the clinical response to RTX in RA at 6 months defined by a good or moderate EULAR response. Methods Patients from the SMART study who signed consent for genetic studies were included (2). The association between the EULAR response at 24 weeks and the polymorphism of the 8 chosen SNPs was analyzed by logistic regression. Response rates were compared across risk genotypes using the χ2 test or the Fisher exact test, when appropriate. Significant variables after univariate regression (P<0.15) were entered into a stepwise multivariate model adjusted to the sex, the age and the DAS28-CRP score. Results Among the 115 included patients, 92 were women, mean age was 56 years, 93 patients were anti-CCP positive. At M6, 30 patients were considered as good responders (26.1%), 62 as moderate responders (53.9%) and 22 as non-responders (19.1%). Univariate analysis showed that IRF5 rs2004640 was significantly associated with a good/moderate EULAR response at week 24 (P=0.038) whereas IRF7 rs1131665 and SPP1 rs9138 were near statistical significance (P=0.092 and P=0.089, respectively). Since it was previously reported an association between TNFSF13B (the gene coding the BAFF cytokine) rs9514828 and RTX response in RA in the same cohort (2), this variant was also included in the multivariate analysis. The multivariate analysis with logistic regression analysis including IRF5, SPP1, IRF7 and TNFSF13B revealed that a genotypic combination of IRF5 rs2004640, SPP1 rs9138 and TNFSF13B rs9514828 was strongly associated with good/moderate response to RTX at M6: P=9.34x10–6, OR =11.37 [4.03–35.28] with a PPV of 91% and a NPV of 53% (Fig. 1). Conclusions We found an association between a combination of type 1-interferon genes and response to RTX treatment in RA. To further validate the magnitude of the association detected an independent replication in a larger cohort is required. If validated, our model could be helpful before the decision of initiating RTX in RA. References Vosslamber S, et al. Ann Rheum Dis 2011. Ruyssen-Witrand A, et al. Rheumatology 2013. Acknowledgement Unrestricted grant from Roche-Chugai and SFR Disclosure of Interest None declared

SAT0208 Inflammatory Myopathies Associated with Sjögren's Syndrome Do Not Differ from Those without Sjögren's Syndrome Aside from Older Age at Diagnosis and Less Frequent Normal Muscle Biopsy

Background Prevalence of Sjogrens syndrome (SS) in inflammatory myopathies (IM) and whether IM patients with SS represent a distinct disease subset are currently unknown. Objectives To assess the signification of SS in IM with regard to phenotype and prognosis. Methods IM patients with SS (IM-SS group) were identified among a cohort of 270 patients with IM using European-American Consensus Group (EACG) classification criteria. Clinical, serological, muscle pathological features, management and outcomes of IM-SS patients were retrospectively studied and compared to the IM patients who had been assessed for SS but did not fulfill these criteria (IM-noSS group). Results EACG criteria were available in 63 IM patients of the total cohort and 29 (46%) were diagnosed as having SS. These IM-SS patients were older at IM diagnosis than the 34 IM-noSS patients (56±3.1 vs 47.7±2.8 years, p=0.05), sex ratio wasnt different. SS was mostly diagnosed at the time of IM diagnosis (n=23, 79%) and less frequently preceded (n=3: 1, 3 and 4 years) or followed (n=3, 3, 6 and 30 years) IM diagnosis. IM-SS patients had subjective sicca syndrome (29/29, 100%) with objective dryness (10/12, 92%), anti-SSA/SSB antibodies (14/29, 48%) and/or focus score ≥3 in minor salivary glands biopsy (n=21/24, 88%). Creatine kinase level was not different between IM-SS and IM-noSS (1400±320 vs 2538±214 UI/L, p=0.5). A normal muscle biopsy was less frequently found in IM-SS than in IM-noSS patient (7/28 vs 1/24 p=0.05). According to the ENMC criteria, DM was the more frequent muscle histological finding in IM-SS patients (n=10, 42%) but all histological patterns were represented (including nonspecific IM: 6 (25%), inclusion body myositis: 4 (17%), polymyositis: 2 (8%), necrotizing myopathy: 1 (4%). This distribution was not different from the IM-noSS group. IM-SS patients also suffered from interstitial lung disease (n=10, 34%), arthralgia and/or arthrithis (n=17, 59%), skin involvement (n=14 48%) and Raynaud syndrome (n=14, 48%) which occurrence characteristics were not different from IM-noSS group. Anti-SSA (n=13, 45% vs n=1, 3%, p=0.0001) and anti-SSB (n=6, 21% vs n=0, 0% p<0.01) were more frequent in IM-SS groups. Other auto-antibodies were found in 14 IM-SS patients (48%) and in 19 IM-noSS patients (56%, p=0.62) which specificities were not significantly different between the two groups. Cryoglobulin was also found with a similar frequency in both groups (n=3, 10% vs n=3, 9%; p=1.0). Six IM-SS patients (21%) were diagnosed with cancer versus 4 IM-noSS patients (12%) (p=0.49). Mean number of treatment was not different between the two groups (1.9±0.2951 vs 1.6±0.2616; p=0.41) and after a follow-up >7 years, 6 patients died in both groups, whithout any significant difference in survival (p=0.23). Conclusions SS is frequently observed in IM. No difference was found between IM-SS and IM-noSS with regards to phenotype, serotype and survival aside from older age at diagnosis and less frequent normal muscle biopsy. Disclosure of Interest None declared