F. Cacciapaglia

Golimumab in real-life settings: 2 Years drug survival and predictors of clinical outcomes in rheumatoid arthritis, spondyloarthritis, and psoriatic arthritis

OBJECTIVES To assess the drug survival of golimumab, and predictors thereof, in patients affected with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA) in a prospective observational cohort. METHODS This is a non-interventional, longitudinal study on RA, SpA, and PsA patients starting treatment with golimumab. Endpoints were the 2 years persistence rate of golimumab and predictors of therapy discontinuation. Drug retention was analyzed using Kaplan-Meier and Cox models. Hazard ratios (HR) of golimumab discontinuation were estimated by Cox-regression hazard models. RESULTS Of 416 patients starting golimumab, 171 biologic-naïve and 245 inadequate responders to prior biologic drugs, 88 had RA, 147 SpA, and 181 PsA. Global 2 years drug retention was 70.2%, with no different hazard of discontinuation among diseases or line of biologic treatment. The strongest predictor of golimumab discontinuation was female gender (HR = 1.95). Golimumab monotherapy was associated with higher risk drug interruption (HR = 1.67). Within SpA, predictors of golimumab discontinuation were female sex (HR = 4.19), and absence of extra-articular manifestations (HR = 4.60). In PsA, duration of disease was negatively associated to drug interruption (HR = 0.93), whereas golimumab monotherapy was positively (HR = 2.21) associated. Interestingly, failing to achieve a good EULAR response at 3 months was the only predictor of golimumab discontinuation for RA patients (HR = 3.03). CONCLUSIONS This study provided evidence that golimumab has high retention rate in real-life settings. SpA male patients with extra-articular manifestations, PsA patients on co-therapy with DMARDs, and RA patients attaining an early clinical response had the highest probability to continue golimumab over 2 years.

The Use of an Interferon-Gamma Release Assay as a Biomarker of Response to Anti-TNF-Alpha Treatment

Postmarketing Phase IV

Lipid profile of rheumatoid arthritis patients treated with anti-tumor necrosis factor-alpha drugs changes according to disease activity and predicts clinical response.

Postmarketing Phase IV

Effective tumour necrosis factor-blocking therapy reduces reactive oxygen metabolite level in rheumatoid arthritis

Objective To assess circulating levels of derived reactive oxygen metabolites (ROMs) in patients with active rheumatoid arthritis (RA), before and during antitumour necrosis factor (TNF)-α therapy. Methods Patients with active RA and failed previous treatment with disease-modifying antirheumatic drugs received subcutaneous anti-TNF-α for 52 weeks. Circulating hydrogen peroxide was quantified as a marker of oxidative stress at baseline and at 24 and 52 weeks. Results The study included 40 patients. Circulating dROM levels were significantly reduced compared with baseline after 24 and 52 weeks’ of anti-TNF-α treatment (33.2 ± 10.0 mgH2O2/dl, 29.5 ± 7.0 mgH2O2/dl and 29.3 ± 9.0 mgH2O2/dl, respectively). There was a significant direct correlation between disease activity score and ROM levels. Conclusion TNF-α inhibition can control disease activity and reduce circulating levels of reactive oxygen species in patients with RA.

Atherosclerosis and Autoimmunity

Abstract Despite a decline in mortality rates in several countries, cardiovascular disease remains the leading cause of death responsible for approximately half of all deaths on the continent. Coronary artery disease and stroke are often the result of acute complications of atherosclerosis (AS) and atherothrombosis. AS is a chronic inflammatory disease, which may have an autoimmune background. Low-density lipoprotein infiltrates and accumulates in the intima of the arterial wall leading to an inflammatory process and the formation of atherosclerotic plaques. These contain lipids but also calcified and fibrotic tissue, vascular cells, cellular debris, and both innate and adaptive immune cells recruited into the arterial wall. When the disruption of an atherosclerotic lesion occurs, thrombus may develop leading to atherothrombosis.

Possible role of adipocytokines in systemic sclerosis–associated small pericardial effusion:

Introduction: Pericardial effusion is a common manifestation of systemic sclerosis, but its pathogenesis has been poorly investigated. Adipokines and interleukins may play a role in the pathophysiology of pericardial effusion. This study aimed at evaluating serum levels of adipokines and interleukins in systemic sclerosis patients with and without pericardial effusion. Methods: A total of 87 systemic sclerosis patients (age 52.6 ± 14 years; disease duration 8.2 ± 6.7 years) were recruited in this study. Demographics, body mass index, and clinical characteristics were recorded in each patient. Pericardial effusion was considered pathologic when ≥50 mL was detected by echocardiography. Serum levels of adiponectin, leptin, resistin, visfatin, tumor necrosis factor-α, interferon-γ, interlueukin-2, interlueukin-10, and interlueukin-17 were measured using Multiplex Immunoassay (Bioplex 200 System). Results: In all, 11 (13%) systemic sclerosis patients had pericardial effusion. Systemic sclerosis patients with and without pericardial effusion did not differ in age, sex, and body mass index. Systemic sclerosis patients with pericardial effusion had significantly higher levels of visfatin (median/interquartile range: 1546 pg/mL (interquartile range: 8590) vs 388 pg/mL (interquartile range: 103), p = 0.03) and interlueukin-17 (1.33 pg/mL (interquartile range: 3.5) vs 0.05 pg/mL (interquartile range: 0.56), p = 0.04), but lower levels of adiponectin (2,845,000 pg/mL (interquartile range: 4,132,900) vs 5,272,100 pg/mL (interquartile range 8,243,600), p = 0.02) than patients without pericardial effusion. Interstitial lung disease, pulmonary arterial hypertension, and “limited” or “diffuse” cutaneous subset did not correlate to adipokines or interleukin levels. Conclusion: Visfatin and adiponectin may play an important role in the pathogenesis of systemic sclerosis–related pericardial effusion. Further longitudinal studies are needed to unravel a possible role of these molecules as biomarkers of pericardial effusion in systemic sclerosis patients.

SAT0307 Impact of the modified rheumatic disease comorbidity index(MRDCI) on drug survival of first line anti-tnfΑ drugs in patents affected with psoriatic arthritis in real life setting

Background Psoriatic Arthritis (PsA) is a chronic condition resulting in significant physical disability and, in many cases, accelerated mortality. Studies have shown that patients with PsA suffer also from associated comorbidities, including cardiovascular diseases, obesity and metabolic syndrome, diabetes, osteoporosis, malignancy and depression; these could also play a role in determining discontinuation from therapy, especially if anti-TNFα drugs are prescribed. Objectives Our study’s goal is to demonstrate the impact of comorbidities on drug survival of first line anti-TNFα treatment in a cohort of patients affected with PsA. Methods We retrospectively assessed 208 patients, (136 female, 72 male) mean age (±SD) 51.35±12.34 years, fulfilling the CASPAR criteria for PsA who underwent first line anti-TNFα therapy in two centres for a mean duration of 23.34±15.50, from 2011 to 2016. Disease characteristics were registered at first entry. To evaluate the burden of comorbidities we used the modified Rheumatic Disease Comorbidity Index (mRDCI),1 a validated score including lung illnesses, cardiovascular diseases, stroke, hypertension, gastrointestinal disorders, diabetes, fractures, depression, obesity, kidney diseases and cancer. The mRDCI was scored at baseline as well. Drug retention was analysed using Kaplan-Maier curves. Cox regression models were used to estimate the inference of mRDCI and several disease characteristics on drug discontinuation. Goodness of fit of the final model was assessed comparing Cox-Snell residuals to Nelson-Alen cumulative hazard function. Results Drug persitence in first line therapy was significantly higher in patients with mRDCI <4 (70.43%) than in those with mRDCI ≥4 (45.45%). Compared to mRDCI ≥4, those with mRDCI <4 showed significantly higher drug survival rate (p=0.018). Multivariate Cox model showed that mRDCI ≥4 (HR 1.94) and female gender (HR 2.39) were strong predictors of drug discontinuation. Nelson–Alen hazard function followed very closely Cox-Snell residuals showed final model fitted well the data except for large values of time.Abstract SAT0307 – Figure 1 Drug survival in first-line anti-TNFα treatment assessed by Kaplan-Meier and comparison among patients with mRDCI <4 and mRDCI ≥4.Abstract SAT0307 – Figure 2 Nelson-Alen Hazard function and Cox-Snell residual Conclusions This study shows that an high mRDCI at baseline negatively impacts the persistence on first line anti-TNFα treatment in patients affected with PsA in real life setting; hence Rheumatologists should take into account comorbidities in the management of PsA and in admninistering anti-TNFα therapy as these may condition the persistence on therapy. Reference [1] Staetgens, et al. Content and construct validity of the Rheumatic Diseases Comorbidity Index in patients with gout. Rheumatology2015Sep;54(9):1659–1663. Disclosure of Interest None declared

AB0709 Switching from originator infliximab to biosimilar infliximab: efficacy and safety in a cohort of patients with established behÇet’s disease

Background Infliximab (IFX) has been proved to be effective in several organ involvement of Behçet’s Disease (BD). A recent report1 describing rapid loss of efficacy of biosimilar IFX after switching from originator IFX suggests the necessity to exercise caution regarding the automatic substitution of originator IFX with biosimilar IFX in patients achieving remission with originator IFX. Objectives The purpose of the present study was to describe our experience with biosimilar IFX CT-P13 in patients affected with BD, who were switched from originator IFX. Methods Retrieved data including demographic characteristics, clinical manifestations and previous treatments were collected. All patients met the ISG and/or ICBD classification criteria for Behçet’s Disease. In order to evaluate disease activity, the BD Current Activity Form (BDCAF) has been evaluated before starting biosimilar, at three, six and nine months after switching to CT-P13. The occurrence of adverse events was also recorded. Wilcoxon matched-pairs signed-ranks test was carried out to evaluate differences between BDCAF distributions pre-switch and either at three, at six and at nine months after switching. Results Thirteen caucasian adult BD patients (mean age 39.77±7.46 years) with a mean disease duration of 12.54±4.21 years, underwent IFX treatment at licensed dosage for a period of 117.66±48.01 months. After 106.92±46.37 months of treatment with originator IFX, all of them were switched to CT-P13 biosimilar IFX. At 3 months after switching, none of them had discontinued CT-P13 biosimilar IFX treatment. No significant difference was noticed between BDCAF mean score assessed at switch and 3 months after switching (p=0.15). At 6 months follow up, 2/13 patients (15.38%) discontinued CT-P13 biosimilar IFX treatment, both for recurrence of mucocutaneous involvement. One out of 2 patients who discontinued CT-P13 IFX had previously experienced a disease flare under originator IFX therapy, requiring a modification of ongoing therapy. BDCAF mean score assessed before and 6 months after switching were not significantly different (p=0.81). Nine months after switching 2 out of the remaining 11 patients were lost at follow up. Once more, no difference was shown between BDCAF mean score assessed at switch and at 9 months follow up (p=0.85). No adverse events occurred during the observed period. Female n(%) 3 (23.08%) Age at Onset (mean±SD) 27.15±10.02 Clinical Manifestations n(%) Uveitis 10 (76.92) Oral Aphtosis 9 (69.23) Genital Aphtosis 7 (53.85) Cutaneous Involvement 7 (53.85) Concomitant Treatment n(%)* Colchicine 5 (38.46) csDMARDs 4 (30.77) Corticosteroids 1 (7.69)Abstract AB0709 – Figure 1 Conclusions Despite the short follow up period, these data suggest that switching BD patients from originator IFX to CT-P13 seems to be effective and safe; only a small percentage of patients experienced relapse of symptoms, whereas a significant modification of BDCAF pre-switch and post-switch was not noticed. Although encouraging, these results need to be confirmed over a longer follow up period and on larger cohorts of patients. Reference [1] Cantini F, et al. (2017) Rapid loss of efficacy of biosimilar infliximab in three patients with Behcet’s disease after switching from infliximab originator. Eur J Rheumatol4 (4):288–290 Disclosure of Interest None declared

OP0129 Drug survival on anti-tnf-alpha in psoriatic arthritis patients with axial involvement and analysis of predictors

Background A few studies have focused on the clinical outcomes in predominant axial Psoriatic Arthritis (PsA) patients treated with anti-TNF-α agents1–3 in real-life settings. Objectives Primary endpoint: to evaluate drug survival on anti-TNF-α agents in PsA patients with axial involvement or axial and either polyarticular or oligoarticular peripheral arthritis. Secondary endpoints: to evaluate the presence of any predictor of discontinuation of anti-TNF in PsA patients with axial involvement and to investigate whether peripheral arthritis may impact the discontinuation for ineffectiveness in patients with axial disease. Methods 415 biologic therapy-naive PsA patients (CASPAR criteria) starting a first TNF-inhibitor from January 2010 to December 2016 were screened. Among these, 87 had axial involvement (ASAS criteria) with imaging arm (X-ray or MRI) and were enrolled: 40 with axial and polyarticular peripheral PsA (Axe +Poly PsA), 38 with axial and oligoarticular peripheral PsA (Axe +Oligo PsA) and 9 with only axial disease (Ax-PsA). At baseline and at last available visit or drug discontinuation, we collected age, gender, disease duration, BMI, HLA-B27, nail psoriasis and/or dactylitis, TJC, SJC, ESR, CRP, enthesitis, LEI, DAPSA, BASDAI, ASDAS-CRP, PASI, HAQ, intake of glucocorticoids and DMARDs, anti-TNF therapy discontinuation and reasons of discontinuation. Drug survival was evaluated by Kaplan-Meier life table method, comparison of survival curves with Log-rank test and baseline predictors of drug discontinuation with Cox regression analysis. Results At baseline, Axe +Poly PsA patients had significantly higher peripheral (DAPSA) and axial disease activity (BASDAI, ASDAS-CRP). Stratifying patients by subset of disease, the median of treatment was 51 months (95% IQR 24.87–77.13) for Ax-PsA group, 50 months (95% IQR 28.39–71.61) for Axe +Oligo PsA group, 30 months (95% IQR 11.84–48.15) for Axe +Poly PsA group (figure 1). Axe +Oligo PsA patients had significantly higher persistence on TNFi rather than Axe +Poly PsA patients (log rank test, p=0.03). Axe +Poly PsA patients had higher risk of stopping TNFi (Cox regression, HR 3.75) and significantly higher percentage of discontinuation for ineffectiveness rather than for an adverse event (χ2 test, p=0.0009). At last observation, Axe +Poly PsA patients had higher DAPSA but no difference in axial disease activity (t-STUDENT test, Mann-Whitney test).Abstract OP0129 – Figure 1 Drug survival on TNF-inhibitor in Ax-PsA, Axe+Oligo-PsA and Axe+Poly-PsA patients (Kaplan-Meier life table method, log rank test) Conclusions PsA subsets seems to have different features, behaviour, clinical response and drug survival on TNF-inhibitors. Axe +Poly PsA subset seems to be more aggressive and difficult to treat. Anti-TNF-α blockers may perform differently in PsA: a more accurate analysis of the clinical disease subsets may improve our knowledge and better management of PsA in daily practice. References [1] Lubrano E, et al. Clin Exp Rheumatol2011Jan-Feb;29(1):80–4. [2] Lubrano E, et al. J Rheumatol2016May;43(5):918–23. [3] Perrotta FM, et al. J Rheumatol2016Feb;43(2):350–5. Disclosure of Interest None declared

AB0618 A unique ultrasound pattern of adipose tissue in systemic sclerosis patients: a comparison with rheumatoid arthritis patients and healthy controls. two sides of adipose tissue involvement in systemic chronic inflammatory diseases

Background Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are both chronic and systemic inflammatory diseases, involving connective tissue. The adipose tissue is acknowledged as an immune organ that secretes numerous inflammatory signals and it is supposed playing an important role in up-regulation of inflammatory status. A few data are published on altered white adipose tissue (WFT) distribution in patients (pts) with RA. None data are available about WFT distribution in SSc pts Objectives We aimed to characterize the subcutaneous adipose tissue (total (sWFT); superficial (SsWFT); inner (IsWFT)) and visceral adipose tissue (vWTF) thickness, evaluated by ultrasound (US) of abdominal adipose tissue, in SSc pts, with different body mass index classes (BMI), comparing with RA pts and healthy controls (HC). Methods 42 SSc pts, 57 RA pts and 12 HC were recruited in this study. WFT measurements were assessed, using US (7.5 MHz probe), along the xiphoumbilican line: sWFT thickness (distance between the inner edge of the skin at the outer edge of the alba line (AL)), SsWFT (lobular upper zone of sWFT), IsWFT (sWFT- SsWFT); vWFT thickness (distance between the inner edge of the AL and the peritoneal line). Results No subject enrolled had metabolic syndrome. RA pts had thicker vWFT (15.6±7.6mm) than SSc pts (10.8±5.8mm) or HC (10.1±3.8mm) (p=0.001). In particular, the upper-weigh RA pts had vWFT 88% thicker than upper-weight HC and the RA obese pts had vWFT 87% thicker than obese HC. While, the upper-weight SSc pts had vWFT 22% thicker than upper-weight HC, and the SSc obese pts had vWFT 16% thicker than obese HC. Positive correlations were found between all WFT measures and BMI in RA pts and HC (p≤0,05). In SSc pts we found lack of correlation between SsWFT and BMI (r=0.232; p=0.145). Of note, only in SSc pts we observed different US WFT patterns (fig. 1a, fig. 1b) characterized by rearrangement of normal sWFT structure (HC fig. 1c and RA pts fig. 1d). These structural rearrangements consisted in the absence of adipose lobules, replaced by hypoechoic – anechoic areas (fig.1a) (attributable to edema), or by hyperechoic lines and spots (fig.1b) (attributable to fibrotic replacement of subcutaneous abdominal fat), independently by SSc diffuse or SSc limited skin subset. Conclusions In SSc and RA the WFT is abnormal. The WFT in RA seems be altered just for dimension and distribution, in particular the vWFT is overexpressed; it might be due to vWFT hyperactivity induced by inflammatory status. In SSc, the WFT is altered in the structure of sWFT. A direct involvement of sWFT in pathologic mechanism of SSc is supposed. An edema phase and a fibrotic phase of abdominal sWFT can be hypothesized, independently by skin involvement. If these findings will be confirmed by fat histological analysis, the US of WFT might be an important tool for the clinicians to identified the earlier stage and/or the active phase (edema) of SSc, in order to support physicians in the decision making about the treatment management. Disclosure of Interest None declared