BackgroundThe antibody-based targeted pharmacodelivery of cytokines by means of immunocytokines has the potential to enhance therapeutic activity at the site of disease while sparing healthy tissues. Dekavil (F8IL10) is a fully human immunocytokine composed of the vascular targeting antibody F8 (specific to EDA) fused to the cytokine interleukin-10. Dekavil is currently in phase II clinical development for the treatment of rheumatoid arthritis (RA).ObjectivesIn the phase Ib dose escalation study, the primary objective was to explore safety, tolerability and the maximum tolerated dose of Dekavil when administered in combination with methotrexate (MTX). The aim of the currently ongoing phase II study is to assess therapeutic activity of Dekavil plus MTX over MTX alone by measuring the mean change from baseline of DAS28-CRP. Immunogenicity of F8IL10 and its PK and PD profile will also be explored.MethodsPatients with active RA despite MTX therapy and who failed anti-TNF treatment are the target population of both studies. In the phase Ib trial, cohorts of 3–6 patients were treated with escalating doses of Dekavil (6, 15, 30, 60, 110, 160, 210, 300, 450 and 600 μg/kg) in combination with a fixed dose of MTX (10–15 mg). In the multicenter, double-blind, placebo-controlled phase 2 study, patients are randomized into two treatment groups (Dekavil 30 or 160 μg/kg plus MTX) and one placebo group (placebo plus MTX). Dekavil is administered once weekly by s.c. injection for a maximum of 8 weeks in both studies.ResultsDekavil has been shown to be well tolerated up to the highest investigated dose (600 μg/kg) and an MTD was not reached. In 33 out of 34 patients treated in the phase 1 study, no DLTs, no SAEs and no SUSARs have been reported. One patient in cohort 9 (450 μg/kg) experienced a DLT (G2 purpura) and a SAE (G2 dyspnea, not drug related). The patient received corticosteroids and fully recovered within one week. Mild injection site reactions were the most frequently observed adverse events and occurred in 62% of the patients. Furthermore, two cases of drug related anemia (G2 and G3) were reported in this study. All adverse reactions resolved completely. At the first efficacy assessment after 4 cycles of treatment, 48% of evaluable patients (16/33) revealed ACR and/or EULAR responses. The fraction of responding patients increased to 57.7% (15/26) after 8 cycles of treatment. Two patients benefited from ACR70 responses for more than 12 months after the last drug administration. As of January 2017, 22 out of 87 patients have been treated in the phase 2 clinical study and neither SUSAR nor treatment-related deaths were recorded.ConclusionsThe currently available data suggest that Dekavil is a safe and promising novel therapeutic for the treatments of RA.Disclosure of InterestM. Galeazzi: None declared, G. Sebastiani: None declared, R. Voll: None declared, J. Wollenhaupt: None declared, O. Viapiana: None declared, J. Dudler: None declared, E. Selvi: None declared, C. Baldi: None declared, M. Bardelli: None declared, B. Bann...

BackgroundThe single-arm non-interventional study ICHIBAN was set up to evaluate the effectiveness and safety of intravenously administered Tocilizumab (TCZ IV) in patients (pts) with moderate to severe rheumatoid arthritis (RA) in Germany. Clinical data were collected during routine medical consultations including concomitant therapies, co-morbidities, therapeutic responses and adverse events.ObjectivesThis interim analysis assessed the effectiveness and safety of long-term TCZ IV treatment with respect to patients' age.MethodsSince February 2010 ∼250 German rheumatology study centres collected these prospective data. Pts were observed for a maximum period of 2 years (104 weeks). The present interim analysis included pts with complete baseline (BL) data before 03rd December 2015 (group total; n=2999). 902 pts have completed the maximal 104 week observation period (group W104). Subgroups according to age have been defined as <50 years, 50–65 years, >65 years.ResultsAt BL the age distribution showed the following proportions: <50 years 28.9%, 50–65 years 48.6%, and >65 years 22.5%. The mean TCZ IV treatment duration was 1.7, 1.8, and 1.7 years, respectively, for the three age groups.In comparison to younger pts, the elderly (>65 years) showed longer disease duration, higher inflammatory parameters, higher disease activity, and higher co-morbidity rates at BL. Nevertheless, TCZ IV showed comparable effectiveness in all age groups. At last visit, DAS28-BSG remission (<2.6) was reached by 55.2%, 51.6%, and 48.8% of pts aged <50, 50–65, and >65 years, respectively. The mean reduction from BL in DAS28-BSG was 2.6, 2.7, and 2.8, respectively.Regarding co-medication, the mean glucocorticosteroid (GC) dose was reduced from 7.1 (BL) to 4.6 mg/d (last visit) and was similar in all subgroups. About 12% of pts stopped GC therapy completely, again similar in all subgroups. At baseline, the rate of TCZ monotherapy (without concomitant sDMARD) was highest in the elderly (53.2%) while combination therapy is more common in younger pts (47.1%). The rate of sDMARD discontinuation while receiving TCZ is comparable in all subgroups (11.5%, 12.1%, 12.3%).Despite slightly higher incidence rates of adverse events (AE) and serious adverse events (SAE) for the elderly, the rates of infections, serious infections and TCZ discontinuation rates due to an AE did not increase with age (Table 1). Gastrointestinal perforation was rarely observed.ConclusionsTCZ IV treatment resulted in improvement of disease activity and reduction in concomitant GC dosing were observed. Despite higher disease burden at baseline, elderly RA patients (>65 years) benefited to the same extent as younger patients, without increased risk of infections. Considering natural age related risks, the low infection and gastrointestinal perforation rates of elderly patients seem to be attributable to the steroid sparing effect of TCZ therapy. Safety concerns should be no reason to argue against anti-IL-6 therapy in elderly patients.Disclosure of InterestC. Specker Consultant for...

BackgroundAntisynthetase syndrome (ASSD) is an autoimmune disease characterised by the clinical triad arthritis, myositis, and interstitial lung disease (ILD). Despite Raynaud’s phenomenon (RP) is another typical feature of ASSD, nailfold videocapillaroscopy (NVC) assessment of these patients has been only sporadically described, without the elucidating data for clinicians.ObjectivesTo describe NVC features of ASSD patients and to investigate possible correlations with clinical and serological features of the disease.MethodsWe retrospectively analysed NVC images of 190 ASSD patients (females/males 3.76, mean age 49.7±12.8 years, mean disease duration 51.2±71.4 months, 133 anti-Jo-1 and 57 non-anti-Jo-1 positive patients). For each patient, we examined number of capillaries, giant capillaries, micro-haemorrhages, avascular areas, ramified capillaries, and the presence of scleroderma (SSc) patterns. Finally, we correlated NVC features with clinical and serological findings of ASSD patients.ResultsNVC abnormalities were observed in 62.1% of AASD patients compared with 29.3% of a group of 75 patients with primary Raynaud’s phenomenon (p<0.001). A SSc-like pattern was detected in 67 (35.3%) patients and it was associated with anti-Jo-1 antibodies (p=0.002) and also with a longer disease duration (p=0.004). Interestingly, there was no significant correlation between the presence of SSc-like pattern and RP, and only 47% of patients with SSc-like pattern had RP.ConclusionsNVC abnormalities are commonly observed in ASSD, independently to the occurrence of RP. The presence of a SSc-like pattern should let to identify a more defined ASSD subtype and prospective studies could confirm the association with clinical and serological features of ASSD.Disclosure of InterestNone declared

Background The ICHIBAN study collects clinical routine data to evaluate the efficacy and safety of tocilizumab (TCZ) in pat. with rheumatoid arthritis (RA) over a period of 2 years. Methods The start of this prospective, non-interventional study, being intended to include 4000 pat., was in Feb. 2010. Clinical data of RA pat., their therapies, therapeutic responses, pat. related outcomes and adverse events are collected “on the fly” using an online database with structured web forms. Results On 18th December 2011 as reference date, baseline data of 1036 pat. were available. In 343 pat. observation period was already at least 52 weeks or discontinuation or change of a treatment was documented. 75.4% of the 1036 pat. were female, the mean age was 56.0 years. Pat. suffered from RA since 10.1 years in mean and the baseline DAS28 was 5.4. 73.3% of the pat. had concomitant diseases. 74.4% were pretreated with TNF-alpha inhibitors, 23.9% exclusively with synthetic DMARDs. In week 52 (LOCF) 31.1% of the pat. (N=97/312) showed a remission of DAS28 (<2,6). A moderate or good EULAR response was seen in 32.3% or 42.2% of the pat., respectively. The mean number of tender joints decreased from 10.1 to 4.4, the mean number of swollen joints from 7.3 to 2.5. The mean ESR decreased from 35.4 to 13.7 mm/1h and the CRP from 3.3 to 0.8 mg/dl. Data on pat. reported outcomes (PRO) and functional status at week 52 are shown in Tab. 1. In 21.9% of the pat. (N=75/343) treatment was changed during the observational period of 52 weeks. The total TCZ exposition was 910.1 pat. years. 781 adverse events were reported (in 339 of the 1036 pat.; 85.8/100 pat. years). 147 of these events were infections (16.2/100 pat. years). 160 serious adverse events were reported (in 95 pat.; 17.6/100 pat. years), 110 of which included an at least improbable causal relationship with TCZ (12.1/100 pat. years). Table 1. Means of VAS scales (mm), FFbH and HAQ Week 0 (Baseline)Week 52 (LOCF)N Disease activity (100 = strongest possible activity)65.240.4249 Health state (100 = very bad)63.041.0248 Exhaustion/fatigue (100 = very strong)60.543.8246 Pain intensity (100 = intolerable pain)65.141.5247 Sleep disturbances (100 = very strong)49.739.8245 FFbH (%)58.664.4249 HAQ1.41.2221 Conclusions The results of this “real life study” represent a severely diseased RA population showing significant impairments. The first 343 patients having completed the first observation period of at least one year show clear improvements in all recorded RA parameters. These data confirm the results of previous real life studies with TCZ such as ROUTINE and TAMARA. The safety results correspond to the expectations. Disclosure of Interest C. Specker Grant/Research support from: Has received honoraria from Chugai for advising in study design and conduction and fees for talks, in summary less than €10.000/year, J. Kaufmann: None Declared, M. Vollmer: None Declared, H. Kellner: None Declared, M. Bohl-Bühler: None Declared, M. Aringer: None Declared, A. Alberding: None Declared, H. Schwenke:...