V Stoica

A3.2 Five year survival rate and predictors of death and disease worsening in a single-center cohort of patients with systemic sclerosis

Background Systemic sclerosis (SSc) is associated with a significant reduction in survival in comparison to the general population. This is the first report on 5-year survival and its predictors in a Romanian cohort of SSc patients. Objective We aimed to assess the 5-year survival rate in a single-center cohort of SSc patients and to identify predictors of death and disease worsening. Methods All patients of the EUSTAR Center 100 enrolled before 2009 and who had at least 2 visits at a minimum interval of 5 years, or who died after at least 3 months of follow-up, were included. All patients were assessed according to current EUSTAR recommendations. A comparison was made between the surviving and the deceased patients regarding all MEDS baseline parameters. Using age-adjusted univariate logistic regression we identified predictors for death and for several outcomes considered as disease worsening: 20% reduction in forced vital capacity (FVC); 20% reduction in diffusing capacity of the lung for carbon monoxide (DLCO); development of pulmonary arterial hypertension (PAH) as assessed by power Doppler heart ultrasound; and digital ulcers (DUs) recurrent at prospective visits. Results Out of 68 patients enrolled before 01.01.2009, 40 met the inclusion criteria (82,5% females, 55% limited cutaneous subset, mean ± SD follow-up period 5.7 ± 2.1 years; mean ± SD age at first visit 49 ± 11.8 years; mean ± SD disease duration at first visit 4.4 ± 6.0 years). Throughout the 5-year follow-up period there were 7 deaths (including 3 SSc-related deaths), resulting in an overall 5-year survival rate of 82,5%. In survivors, lung function tests deteriorated significantly in 11% (FVC) and 52% (DLCO), while 20% developed PAH. Recurrent or newly appearing DUs occurred in 21% of all 42 patients. Significant predictors for death were the diffuse cutaneous subset, and the presence of DUs at presentation, with odd ratios [95% confidence interval] (OR[CI95%]) of 14,2 [1.3-151] and 38 [2.9-501] respectively. Conduction blocks on the baseline ECG predicted PAH with an OR [95% CI] of 12.8 [1.5-108]. Significant predictors for DUs were active DUs and calcinosis at presentation: OR [CI95%] 5.2 [1.1-26] and 6 [1.1-33] respectively. None of the parameters tested as potential predictors of the respiratory function decline achieved statistical significance. Conclusions The survival rate in our cohort was 82.5%, which is similar to other cohorts from developed countries. We identified diffuse cutaneous subset, active digital ulcers, and heart conduction blocks as predictors for a poor disease outcome.

SAT0681 Risk of active tuberculosis in patients with inflammatory arthritis receiving tnf-inhibitors

Background Tuberculosis (TB) is a major concern in patients receiving TNF inhibitors (TNFi). Objectives To assess the incidence of active TB and the efficacy of TB prevention measures in a large, single-center cohort of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) receiving TNFi. Methods Data of all patients in whom treatment with TNFi was initiated in our rheumatology clinic from January 1st 2002 until December 31st 2015 have been retrospectively analysed. The cohort was divided into 2 groups per the mandatory latent TB infection (LTBI) screening method at baseline: tuberculin skin test (group TST), and QuantiFERON®-TB Gold test (group QFT). The incidence of active TB was analysed for each group and compared to TB incidence data in general population. Results 653 patients were included (344 RA, 52 PsA, 257 AS); 324 patients belonged to the TST and 329 to the QFT group. The number of active TB cases/ time of exposure to TNFi (person-years, PY) was 17/2002.6 and 7/1041.2 respectively, accounting for an incidence of 848.9 and 672.3 cases per 105 PY, about 8 times higher (8.3 and 8.8 for TST, respectively QFT group) than the average TB during the period of exposure to TNFi. LTBI reactivations per total TB cases were only 4/17 and 2/7, respectively, too few to identify statistically significant differences between the 2 LTBI screening protocols. Only 10 patients had pulmonary TB, whereas the rest were disseminated TB (8 cases), TB pleurisy and/or pericarditis (4 cases), one mediastinal lymph node TB and one isolated hepatic TB. Using Pearson chi-square test, we found no significant differences between LTBI group and active TB (Table 1).Table 1. LTBI screening results and TB occurrence in the 653 TNFi-treated patients (Pearson χ2 test) TST QFT All p value (n=324) (n=329) (n=653) Positive immuno-diagnostic test at baseline 52 (16.0%) 63 (19.1%) 115 (17.6%) <0.001* Active TB 17 (5.2%) 7 (2.1%) 24 (3.7%) 0.185* Reactivation TB 4 (1.2%) 2 (0.6%) 6 (0.9%) ** New infection TB 13 (4.0%) 5 (1.5%) 18 (2.8%) 0.052* Total TB incidence (per 105 PY) 848.9 672.3 788.5 – Maximal period of TNFi exposure in group 2002–2016 2011–2016 2002–2016 – Mean TB incidence in Romania in the respective time period (per 105 PY) 102.3 76.7 102.3 – TB incidence patients/general population 8.3 8.8 7.7 0.88† *Pearson χ2test comparing TST and QFT. **Reactivation TB cases were too few to perform statistical testing. †Pearson χ2test comparing total TB incidence in the TST and QFT groups to the average TB incidence in our region in the respective period of exposure. Conclusions In our cohort, new infection TB exceeds reactivation TB, suggesting the necessity of periodical LTBI re-screening. Disclosure of Interest A. M. Gheorghiu: None declared, A. Garaiman: None declared, A. Radu: None declared, A. Soare: None declared, V. Aramă: None declared, D. Bumbăcea: None declared, R. Dobrotă: None declared, R. Oneata: None declared, S. Pintilie: None declared, M. Milicescu Speakers bureau: Has received sponsoring from Abbvie, MSD and Pfizer., I. Ancuta Grant/research support from: Abbvie, Pfizer, Roche, UCB, BMS, Consultant for: Abbvie, Pfizer, Roche, UCB, BMS, Speakers bureau: Abbvie, Pfizer, Roche, UCB, BMS, A. Martin Grant/research support from: Abbvie, MSD, Pfizer, Roche, UCB, BMS, M. Sasu Grant/research support from: Abbvie, MSD, Pfizer, Roche, UCB, BMS, C. Ciofu Grant/research support from: Abbvie, MSD, L. Macovei Grant/research support from: MSD, Pfizer, Roche, V. Stoica: None declared, M. Bojinca Grant/research support from: Abbvie, MSD, Pfizer, Roche, UCB, BMS, Consultant for: Abbvie, MSD, Pfizer, Roche, UCB, BMS, Paid instructor for: Abbvie, MSD, Pfizer, Roche, UCB, BMS, C. Mihai Grant/research support from: Abbvie, MSD, Pfizer, Roche, UCB, BMS, Consultant for: Abbvie, MSD, Speakers bureau: Abbvie, MSD, Pfizer, Roche, UCB, BMS

SAT0211 Reliability, Validity, and Sensitivity to Change of The Duruoz Hand Index in Systemic Sclerosis

Background Hand involvement is observed in almost all patients with Systemic Sclerosis (SSc), and is due to skin and tendon fibrosis, arthritis and microvascular impairment, sometimes complicated with digital ulcers (DUs). Objectives The Duruozs Hand Index (DHI) (or Cochin hand functional disability scale), is a reliable tool for hand function assessment and can be used in diseases like rheumatoid arthritis and SSc. The purpose of this study was to assess the reliability, validity and sensitivity to change of the DHI in SSc patients. Methods 66 patients with SSc according to the 2013 ACR/EULAR criteria, examined in our EUSTAR center from 1.10.2014 to 31.12.2015 were included. Patients completed the DHI, the Scleroderma Health Assessment Questionnaire (SHAQ) questionnaires and the Hand Mobility in Scleroderma (HAMIS) test. Three anthropometric measures to assess finger range of motion were also measured: the finger extension (FE), finger-to-palm distance (FTP) and Δ FTP (FE - FTP). Step 1: In 38 patients the test-retest reliability, using intra-class correlation coefficients (ICC), and the internal consistency (Cronbachs alpha test) were examined. Step 2: In all 66 patients, the criterion validity by correlation coefficients with SHAQ, HAMIS and the anthropometric measures, and the discriminative capacity between different subsets of patients were examined. Step 3: 27 consecutive patients had a second evaluation at an interval of (mean±SD) 9.3±2.3 months; among them, only 4 patients had progressive early diffuse SSc. Sensitivity to change was assessed in these patients using the effect size (ES) (Cohens d) and the standardized response mean (SRM). Results The study included 59 females/7 males with SSc, age 50.8±13.0 years, disease duration 6.2±6.0 years; 24 with diffuse cutaneous SSc (dcSSc) and 38 with limited cutaneous SSc (lSSc). The DHI had a mean±SD score of 22.8±19.5, range 0–71 (with possible range 0–90) at baseline, and 24.3±21.1, range 0–73 at follow-up. The DHI presented an excellent test-retest reliability (ICC 0.98), a good internal consistency (Cronbachs alpha 0.960). Criterion validity of the DHI was proved by moderate to strong correlations with HAMIS, FE, FTP, Δ FTP and the SHAQ disability index (Spearman rho 0.57–0.85, p<0.001). The discriminative capacity of the DHI was proven by statistically significant differences between patients with and without: synovitis, flexion contractures of the fingers, and history of DUs. The sensitivity to change (ES of 0.27 and SRM of 0.52) was acceptable for detecting the minimally important difference. Conclusions The DHI is a reliable, valid and easy to apply tool for hand involvement assessment in patients with SSc. The preliminary results on sensitivity to change suggest DHI could be a sensitive measure to detect change in clinical status, however more early diffuse SSc patients are needed to confirm these findings. Acknowledgement *This abstract was realized as part of the “Development of a computer-based nailfold videocapillaroscopy (NVC) system for longitudinal evaluation of patients with systemic sclerosis” (QUANTICAP) project, financed by the UEFIS-CDI PN-II-PT-PCCA-2013–4-1589 grant. Disclosure of Interest None declared

THU0331 Increased Incidence of Tuberculosis Among Systemic Lupus Erythematosus Patients – Should Tuberculosis Screening at Diagnosis be the Next Step?

Background World Health Organization (WHO) declared tuberculosis (TB) the most common infectious disease in the world. TB has a higher incidence among patients with systemic rheumatic diseases than in the general population; in such patients, it frequently presents as extrapulmonary or disseminated disease. According to WHO surveillance reports, although steadily decreasing during the last years, the incidence of TB in Romania in 2005-2014 was by far the highest among all EU countries. Objectives To assess the characteristics and risk factors of active TB infection in a cohort of patients with systemic lupus erythematosus (SLE). Methods Data of all SLE patients followed up in our clinic in 2005 – 2014 were retrospectively analyzed. Clinical and demographic characteristics and treatment before diagnosis of TB were recorded. The incidence of active TB infection was compared to data from the general population. Univariable logistic regression was used to assess the influence of various factors on the risk of developing TB. Results Four hundred SLE patients were evaluated in our clinic during the 10-year interval; of them, 18 cases of active TB per 4291 patient-years (time of exposure, PY) were identified, accounting for an incidence of 419.5/100.000 PY, which is 4.43 times the incidence of TB in our region in the period 2005-2014. Ten of the 18 cases had extrapulmonary or disseminated TB; delayed diagnosis and more severe forms were observed in them. Two patients repeatedly had active TB infection after 2, respectively 3 years from the first TB diagnosis. High-dose glucocorticoids (hd-GC) and cyclophosphamide (CYC) treatment were significantly associated with TB: OR (95% CI) 9.6 (1.2-77.5), p=0.03 for hd-GC and 3.3 (1.2-9.1), p=0.02 for CYC. Fever was the most important red-flag for the diagnosis of TB, OR (95% CI) 73.1 (15.2-352.7), p<0.001. Other frequent manifestations were weight loss and cough. No association was found between TB and age, disease duration or socio-economic status. Conclusions We found an increased incidence of active TB infection with a majority of extrapulmonary TB in a large cohort of Romanian SLE patients. Cyclophosphamide treatment and high daily dose of glucocorticoids before the diagnosis of TB were important determinants for the increased risk of TB in SLE patients. These results suggest that in a country with high TB burden, TB screening and treatment of latent TB would be useful before initiation of immunosuppressive treatment. Disclosure of Interest None declared

SAT0330 Active Tuberculosis in Arthritis Patients Receiving TNF Inhibitors Despite Baseline Screening

Background Screening for active and latent Tuberculosis (TB) is mandatory before TNF inhibitors (TNFi) initiation but despite all efforts made, TB still remains a major concern in these patients, especially in countries with a high TB burden. Objectives To assess the incidence of active TB and the efficacy of TB prevention measures in a cohort of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) receiving TNF inhibitors, in a Romanian academic rheumatology center. Methods Data of all patients who received treatment with TNFi in our clinic between 01.2001 and 01.2015 have been retrospectively analyzed. Demographic characteristics, baseline TB screening results, TB prophylaxis, exposure time to TNFi, and active TB cases were extracted from clinical records. Mandatory TB screening procedure at baseline included tuberculin skin test (TST) between 01.2001- 08.2010 (positive when >10 mm until 12.2004 and >5mm from 01.2005) and QuantiFERON®-TB Gold test (QTF) from 09.2010 to present. The cohort was divided into 3 groups, according to the TB screening method (TST1: 01.2001-12.2004, TST2: 01.2005-08.2010 and QTF: 09.2010-01.2015) and the frequency of active TB was analyzed. Latent TB reactivation (LTBR) was defined as TB occurring in the first 12 months of treatment. The influence of the screening method on active TB incidence was assessed using Cox proportional hazard regression. Results 550 patients were included (305 RA, 42 PsA, 203 AS): 78 in TST1, 249 in TST2 and 223 in the QTF group. Baseline screening test was positive in 3.8% patients in TST1 group, 17.67% in TST2 group and 18.3% in QTF group. None of the patient receiving TB prophylaxis developed active TB. The number of active TB cases/time of exposure to TNFi in the 3 groups was 9/468.83, 9/1066.91 and 3/551.45 respectively, accounting for an incidence of 1919.67, 843.55 and 544.02 cases per 105 person years (PY). The incidence of TB in Romania, as reported to the World Health Organization, decreased from 147 to 94 per 105 PY from 2001 to 2012. Cases considered to be LTBR/total TB cases in TST1, TST2 and QTF groups were 2/9, 2/9 and 1/3 respectively, while the rest of them were appointed as new TB infection. Using Cox regression adjusted for age at TNFi initiation, sex, disease and treatment, we found no influence of the TB screening method on the risk of LTBR. However, the TST2 and QTF groups had a significantly lower TB risk, with the TST1 group as reference, when all cases of active TB were analyzed: HR [95% CI] were 0.19 [0.04-0.94], p=0.041 for TST2 and 0.09 [0.01-0.74], p=0.025 for QTF, suggesting that the period of TNFi initiation, when the TB incidence in general population was higher than in the later years, determined a higher risk for active TB. Conclusions In a country with a high TB burden, where all arthritis patients started on TNFi were screened for latent TB, new TB infection exceeds LTBR. Baseline screening and prophylaxis was efficient in positive patients but it is not enough in preventing active TB on a long term and the screening protocol should be revised. Disclosure of Interest None declared

THU0413 Preventing Active Tuberculosis in Rheumatoid Arthritis Patients Receiving TNF Inhibitors: TB Screening at Baseline is not Enough

Background Tuberculosis (TB) is a major concern in patients treated with TNF inhibitors (TNFi), especially in countries with a high TB burden. Careful screening for active and latent TB is mandatory before TNFi initiation, and patients with latent TB receive prophylactic treatment, however this does not influence the risk of TB reinfection/new infection. Objectives To assess the incidence of active TB and the efficacy of TB prevention measures in a cohort of rheumatoid arthritis (RA) patients receiving TNFi, in a Romanian academic Rheumatology center. Methods Data of all RA patients who received treatment with TNFi in our clinic between 2001 and 2013 have been retrospectively analyzed. Demographic characteristics, baseline TB screening results, TB prophylaxis, duration of TNFi treatment, and reported active TB were documented. The cohort was divided into 3 groups according to the mandatory TB screening method at baseline: tuberculin skin test (TST) with a positive threshold of either >10mm (01.2001-12.2004) = group TST1, or >5mm (01.2005-08.2010) = group TST2, and QuantiFERON®-TB Gold test (09.2010-12.2013) = group QTF. All patients tested positive for latent TB received prophylaxis with isoniazide for 9 months. The incidence of active TB was analyzed for each group and compared to TB incidence data in Romanian general population, which were retrieved from the World Health Organization (WHO) statistic reports. The influence of the screening method on active TB incidence was assessed using Cox proportional hazard regression. Results 304 RA patients were included: 50 in TST1, 159 in TST2 and 95 in the QTF group. The number of active TB cases/the time of exposure to TNFi in person-years (PY) in the 3 groups was 6/322.6, 5/708.8 and 1/133.2 respectively, accounting for an incidence of 1860, 705 and 751 cases per 100,000 PY. The incidence of TB in Romania, as reported to the WHO, decreased from 147 to 94 per 100,000 PY from 2001 to 2012. When analyzing the duration from TNFi initiation to the diagnosis of active TB, only 2/6 cases in TST1 and 1/5 cases in TST2 had less than 6 months (latent TB activation), while all other cases were diagnosed after over 12 months (probably new infection). There was no influence of the TB screening method on the risk of active TB: hazard ratios [95% confidence interval] were 0.34[0.10-1.13] for TST2 and 0.25 [0.03-2.24] for QTF, both p>0.05, when TST1 was the reference group. Similarly, there were no significant differences when comparing groups with regard to latent TB reactivation or to new TB infection. Comparing the QTF group to the combined TST1+TST2 groups led to similar results. Conclusions In a country with a high TB burden, where all RA patients started on TNFi are screened for latent TB before treatment initiation, new TB infection exceeds latent TB reactivation. TB incidence in these patients is much higher than in the general population and screening at initiation does not solve the problem of later infection. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3653