H.M. Lorenz

FRI0318 Two-Year Retention and Effectiveness of IV Abatacept in Real-Life Setting: Results from the Action Study

Background Initial results from the real-world ACTION study suggest that abatacept (ABA) is clinically effective and well tolerated in pts with RA, with good pt retention over 12 mths.1 Objectives To assess retention rates and the effectiveness of IV ABA over 24 mths in the ACTION study. Methods ACTION is a 2-yr, international (Austria, Belgium, Canada, Czech Republic, Denmark, Germany, Greece, Italy, the Netherlands), non-interventional cohort of pts with RA who initiated IV ABA between May 2008 and January 2011. ABA retention (and 95% CI) over 24 mths was estimated by Kaplan–Meier and stratified by previous RA therapy. The proportion of pts achieving a moderate or good EULAR response was assessed in pts on ABA at 24 mths (as observed). Safety is reported for all enrolled pts. Results 1137 pts were enrolled and 1131 pts were evaluable; 122 (10.8%) patients were biologic-naïve and 1009 (89.2%) had failed ≥1 prior biologic agent (out of which, 487/1009 [48.3%] failed 1 anti-TNF and 504/1009 [50.0%] ≥2 anti-TNFs, while 18/1009 [1.8%] failed non anti-TNFs only). Baseline characteristics were similar, but disease duration was numerically shorter in biologic-naïve pts versus pts failing ≥1 prior biologic agent (7.0 vs 11.8 yrs). The overall retention rate (95% CI) at 24 mths was 54.4% (51.3, 57.4). Retention rates at 24 mths were higher in biologic-naïve pts (63.2% [53.2, 71.6]) and pts who failed 1 prior anti-TNF (60.6% [55.9, 64.9]) versus pts failing ≥2 prior anti-TNFs (46.7% [42.0, 51.2]) (Figure). The retention rate was 49.2% (44.0, 54.1) in pts who had failed 2 previous anti-TNFs (n=410) and 35.5% (25.4, 45.7) in pts who failed 3 previous anti-TNFs (n=94). More pts discontinued in later lines of treatment for inefficacy (23.9% in biologic-naïve pts and 35.7% in pts failing ≥1 prior biologic agent) than intolerance/safety (7.0% and 10.6%, respectively). A good or moderate EULAR response was achieved in 95.0% of biologic-naïve pts (n=20) and in 80.2% of pts failing ≥1 prior biologic agent (n=283). There were 111 serious adverse events in 63/1137 (5.5%) pts (28 discontinuations) and 12 deaths, including 4 due to serious infections (sepsis [4 mths after last ABA infusion; pt was receiving tocilizumab]; Pneumocystis jiroveci [4 mths after last ABA infusion, pt had deep vein thrombosis]; pneumonia and urosepsis unrelated to ABA). Serious infections occurred in 26 pts and there were 12 malignancies, 5 serious cardiac disorders and 1 serious hypersensitivity reaction. No TB occurred and 2 opportunistic infections were reported (Cytomegalovirus and P. jiroveci). Conclusions In this real-world setting study, more than 50% of patients retained IV abatacept over 2 years. Higher long-term retention rates were observed when abatacept was initiated earlier in the course of RA. In ACTION, IV abatacept was clinically effective and well tolerated in a broad range of bioexperienced patients. References Nüβlein H, et al. Arthritis Rheum 2012;64(Suppl10):S199. Disclosure of Interest H. Nüβlein Consultant for: Bristol-Myers Squibb, Abbott, Chugai, UCB, Essex, Wyeth, Pfizer, MSD, Novartis and Roche, Speakers bureau: Bristol-Myers Squibb, Abbott, Chugai, UCB, Essex, Wyeth, Pfizer, MSD, Novartis and Roche, R. Alten Grant/research support: BMS, Speakers bureau: BMS, M. Galeazzi: None declared, H.-M. Lorenz Consultant for: BMS, Speakers bureau: BMS, M. Nurmohamed Grant/research support: The Jan van Breemen Research Institute has received research grants from Roche, Abbott, Pfizer, UCB and BMS, Consultant for: Roche, Schering-Plough, BMS, UCB, Wyeth, Pfizer and MSD, Speakers bureau: Abbott, Roche, Pfizer and BMS, W. Bensen Grant/research support: Abbott, Amgen, BMS, Janssen, Merck, Lilly, Novartis, Pfizer, Proctor and Gamble, Roche, Sanofi-Aventis, Schering, Takeda, UCB, Warner Chilcott, Wyeth, Consultant for: Abbott, Amgen, BMS, Janssen, Merck, Lilly, Novartis, Pfizer, Proctor and Gamble, Roche, Sanofi-Aventis, Schering, Takeda, UCB, Warner Chilcott, Wyeth, Speakers bureau: Abbott, Amgen, BMS, Janssen, Merck, Lilly, Novartis, Pfizer, Proctor and Gamble, Roche, Sanofi-Aventis, Schering, Takeda, UCB, Warner Chilcott, Wyeth, G.-R. Burmester Grant/research support: Clinical trials for BMS, AbbVie, Pfizer, Medimmune, Novartis, Roche, UCB, Lilly, Consultant for: BMS, AbbVie, Pfizer, MSD, Medimmune, Roche, UCB, Speakers bureau: BMS, Abbott, Pfizer, MSD, Roche, UCB, H.-H. Peter: None declared, K. Pavelka Grant/research support: MSD, Pfizer, Amgen, AbbVie, Roche, Consultant for: MSD, Pfizer, Amgen, AbbVie, Roche, M. Chartier Consultant for: BMS, C. Poncet Consultant for: BMS, C. Rauch Employee of: BMS, M. Le Bars Shareholder of: BMS, Employee of: BMS DOI 10.1136/annrheumdis-2014-eular.1750

FRI0394 The Proteasome Inhibitor Bortezomib Ameliorates Refractory Systemic Lupus Erythematosus (SLE): A Prospective Multi-Centre Observational Study

Objectives The proteasome inhibitor bortezomib, approved for the therapy of multiple myeloma, depletes plasma cells (PCs) and ameliorates nephritis in mouse models of systemic lupus erythematosus (SLE). Here, we analyzed the efficacy of bortezomib as induction therapy in patients with refractory SLE. Methods Twelve patients with active SLE were included in this prospective multicentre cohort study. The patients received one to four cycles of intravenous bortezomib (Velcade®) 1.3mg/m2 as “off-label” treatment. Disease activity was evaluated using the SELENA-SLEDAI score. We determined serum concentrations of anti–double-stranded DNA (anti-dsDNA) and protective antibodies. Multicolor flow cytometry was performed to analyze peripheral blood B and PC subsets as well as Siglec-1 expression on monocytes as surrogate marker for type I interferon (IFN) activity. Results The disease activity significantly decreased upon induction therapy with bortezomib and remained stable for the following 3 months under maintenance therapies. Treatment-related adverse events were mild or moderate. During proteasome inhibition, serum antibody concentrations significantly declined with greater reductions in anti-dsDNA (∼60%) than protective (∼30%) antibodies. Upon bortezomib treatment, numbers of HLA-DR+ short-lived (p=0.024) and HLA-DR– long-lived (p=0.038) peripheral blood PCs were strongly decreased, whereas circulating B cells remained virtually unaffected. Notably, PC numbers significantly increased in-between cycles. Siglec-1 expression on monocytes significantly declined (p<0.001) indicating reduced type 1 IFN activity. Conclusions Bortezomib targeting PCs and type I IFN activation may represent an effective treatment option with rather low toxicity in refractory SLE patients. Bortezomib efficiently induces short-term remissions but requires maintenance treatment inhibiting PC regeneration for sustained efficacy. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5884

SAT0227 Two-Year Retention and Effectiveness of IV Abatacept Monotherapy and Combination in PTS with RA Previously Treated with at Least One Biologic Agent in A Real-Life Setting: Subgroup Analysis from the Action Study

Background Although biologic agents should be preferentially used in combination with MTX or other conventional synthetic (cs)DMARDs,1 monotherapy with a biologic may be considered, especially if there is an intolerance to csDMARDs. Objectives To assess retention rates and the effectiveness of IV abatacept (ABA) in monotherapy or in combination with csDMARDs (±MTX) over 2 yrs in the real-world ACTION study. Methods ACTION is a 2-yr, international (Austria, Belgium, Canada, Czech Republic, Denmark, Germany, Greece, Italy, the Netherlands), non-interventional cohort of RA pts who initiated IV ABA between May 2008 and January 2011. ABA retention (and 95% CI) over 24 mths was estimated using the Kaplan–Meier method. Pts who failed ≥1 biologic agent were grouped by treatment pattern at ABA initiation (monotherapy vs combination [± MTX]). The proportion of pts achieving a moderate or good EULAR response was assessed in pts on ABA at 24 mths (as observed). Results The analysed population comprised 1131 pts; 1009 (89.2%) pts had failed ≥1 biologic agent. ABA was initiated in combination with csDMARDs in 772/1009 (76.5%) pts (MTX in 569/1009 [56.4%] pts) and as monotherapy in 237/1009 (23.5%) pts. Compared with combination, pts in the monotherapy group were older (mean [SD]: 59.1 [12.5] vs 55.3 [12.2] yrs), had longer disease duration (13.9 [10.6] vs 11.2 [8.7] yrs), more comorbidities (77.2 vs 70.6%) and had failed a greater number of anti-TNFs (57.4 vs 47.7% failed ≥2 previous anti-TNFs). In the monotherapy group, previous MTX was discontinued due to intolerance in 68.1% of pts. A total of 161/237 (67.9%) pts were receiving a biologic agent as monotherapy when they switched to ABA. Retention rates at 24 mths were similar for the combination and monotherapy groups (Figure). Similar proportions of pts discontinued ABA for lack of efficacy (34.4 vs 40.0%) or intolerance (9.7 vs 13.7%) in both combination and monotherapy groups, respectively. A good or moderate EULAR response was achieved in 80.6% of pts in the combination group (n=222) and in 78.8% of pts in the monotherapy group (n=61). The safety and tolerability of ABA in the total population are reported elsewhere and were consistent with previously published data.2 Conclusions Over 24 mths in a real-life setting, good retention rates were observed with IV abatacept in pts refractory to previous biologic agents. Retention rates were similar when abatacept was initiated in combination with csDMARDs or with concomitant MTX. Retention rates with abatacept monotherapy were similar to combination, although patients on monotherapy had more comorbidities and most were intolerant to MTX, supporting monotherapy use in these patients. References Smolen J, et al. Ann Rheum Dis 2013, doi: 10.1136/annrheumdis-2013-204573. Nüßlein H, et al. Arthritis Rheum 2012;64(Suppl10):S199. Poster 460. Disclosure of Interest H. Nüβlein Consultant for: Bristol-Myers Squibb, Abbott, Chugai, UCB, Essex, Wyeth, Pfizer, MSD, Novartis, Roche, Speakers bureau: Bristol-Myers Squibb, Abbott, Chugai, UCB, Essex, Wyeth, Pfizer, MSD, Novartis, Roche, R. Alten Grant/research support: BMS, Speakers bureau: BMS, M. Galeazzi: None declared, H.-M. Lorenz Consultant for: BMS, Speakers bureau: BMS, M. Nurmohamed Grant/research support: The Jan van Breemen Research Institute has received research grants from Roche, Abbott, Pfizer, UCB and BMS, Consultant for: Roche, Schering-Plough, BMS, UCB, Wyeth, Pfizer and MSD, Speakers bureau: Abbott, Roche, Pfizer and BMS, W. Bensen Grant/research support: Abbott, Amgen, BMS, Janssen, Merck, Lilly, Novartis, Pfizer, Proctor and Gamble, Roche, Sanofi-Aventis, Schering, Takeda, UCB, Warner Chilcott, Wyeth, Consultant for: Abbott, Amgen, BMS, Janssen, Merck, Lilly, Novartis, Pfizer, Proctor and Gamble, Roche, Sanofi-Aventis, Schering, Takeda, UCB, Warner Chilcott, Wyeth, Speakers bureau: Abbott, Amgen, BMS, Janssen, Merck, Lilly, Novartis, Pfizer, Proctor and Gamble, Roche, Sanofi-Aventis, Schering, Takeda, UCB, Warner Chilcott, Wyeth, G.-R. Burmester Grant/research support: CClinical trials for BMS, AbbVie, Pfizer, Medimmune, Novartis, Roche, UCB, Lilly, Consultant for: BMS, AbbVie, Pfizer, MSD, Medimmune, Roche, UCB, Speakers bureau: BMS, Abbott, Pfizer, MSD, Roche, UCB, H.-H. Peter: None declared, K. Pavelka Grant/research support: MSD, Pfizer, Amgen, AbbVie, Roche, Consultant for: MSD, Pfizer, Amgen, AbbVie, Roche, M. Chartier Consultant for: BMS, C. Poncet Consultant for: BMS, C. Rauch Employee of: BMS, M. Le Bars Shareholder of: BMS, Employee of: BMS DOI 10.1136/annrheumdis-2014-eular.1816

SAT0623 Clinical features and treatment of idiopathic recurrent acute pleuro-pericarditis

Background Idiopathic recurrent acute pleuro-pericarditis (IRAP) is an increasingly recognised autoinflammatory disease comprising post-pericardiotomy-syndrome, recurrent pericarditis and post-myocardial-infarction-syndrome. Different autoimmune mechanisms were discussed in the past. Recently, IRAP is considered as an autoinflammatory disease. Therapeutic options comprise colchicine, prednisolone and interleukin (IL)−1beta blockingagents. Objectives to investigate whether idiopathic and post-interventional pleuro-pericarditis represent a clinical spectrum and to identify treatment options. Methods This study analyses demographic, clinical and laboratory features of post-interventional and idiopathic pleuro-pericarditis and adult onset Still’s disease (AOSD) as a reference. Patients with infectious disease, connective tissue disease, chronic heart failure, renal failure and other non-exsudative effusions were excluded from this analysis. Patients with IRAP were treated with colchicine, prednisolone and IL1β blocking agents. Results Between 2005 and 2017 66 cases of idiopathic and post-interventional pleuro-pericarditis were identified and compared to 83 cases of AOSD. Clinical and laboratory features suggest that idiopathic and post-interventional pleuro-pericarditis represent a clinical spectrum which is identical with IRAP. Prednisolone was started with 25 mg to 125 mg and tapered to less than 7 mg or discontinued if not effective. 47 of 66 patients (71%) were treated with prednisolone and 10/47 (21%) were in remission with no need of any further therapeutically escalation. Colchicine was given to 44/66 patients (67%) and 29/44 (66%) were in complete remission. Four of 66 patients (6%) did not respond or had contraindications against colchicine or prednisolone and were treated with anakinra. Of these patients 4/4 (100%) were in remission. During the follow-up period of 20 patient*months 2 of 4 patients maintained the remission with anakinra every 2nd day and two patients discontinued anakinra and remained in remission. Conclusions 1. post-pericardectomy-syndrome, post-myocardial-infarction-syndrome and idiopa-thic recurrent pericarditis represent a clinical spectrum of autoinflammatory diseases. 2. treatment options comprise colchicine as a first-line therapy, prednisolone and anti-IL1 blocking agents. Acknowledgements none. Disclosure of Interest None declared

FRI0245 Abatacept retention rates and prognostic factors of retention in patients with rheumatoid arthritis: 2-year results from the real-world action study

Background The ACTION (NCT02109666) study was designed to provide prospective, real-world data on abatacept (ABA) retention in patients (pts) with RA. Objectives To assess the retention rate and to identify prognostic factors of ABA retention in the overall ACTION population and by treatment line over 2 yrs. Methods ACTION is a 2-yr, international, observational study of pts with RA who initiated IV ABA as first- or as second-/further-line biologic therapy in routine clinical practice. Biologic-naïve and biologic-failure pts were enrolled during three periods between May 2008 and December 2013. The primary endpoint was crude ABA retention rate over 2 yrs (Kaplan–Meier plot). Prognostic factors (p≤0.2) from univariate analyses with no colinearity, clinically relevant variables and known risk factors were entered into a multivariate model; factors with p≤0.1 were retained by backward selection. EULAR response was compared by Fishers exact test. Results In the ACTION cohort, 2350/2364 enrolled pts were evaluable for analysis; 673 (28.6%) were biologic naïve and 1677 (71.4%) had failed biologic treatment. Most biologic-failure pts (56.6%) had previously received ≥2 biologics. Some expected differences in baseline characteristics were observed between groups; mean (SD) RA duration was shorter (7.2 [8.2] vs 12.1 [9.1] yrs; p<0.001), more pts had RA for ≤2 yrs (35.7 vs 9.0%; p<0.001) and fewer pts had radiographic erosions (58.2 vs 71.5%; p<0.001) for biologic-naïve vs biologic-failure pts. At Yr 2, the overall retention rate was 47.9% (95% CI 45.7, 50.0). The retention rate was higher in biologic-naïve vs biologic-failure pts (54.5 vs 45.2%; p<0.001) and in pts with 1 vs ≥2 previous biologics (Fig). Reasons for discontinuation were comparable between groups; main reasons were lack of efficacy (61.4 vs 67.7%) and safety (21.3 vs 21.2%). RF and anti-citrullinated protein antibody (ACPA) seropositivity were prognostic factors for higher retention in biologic-naïve (p=0.030) and biologic-failure pts (p=0.028); other positively impacting factors were diabetes mellitus (p=0.044; biologic naïve); geographic location (p<0.001; biologic naïve) and ABA combination therapy (p<0.001; biologic failure). Only Pt Global Assessment (p=0.009; biologic failure) predicted lower retention. Among pts continuing ABA, a greater proportion of biologic-naïve vs biologic-failure pts had a good/moderate EULAR response (90.7 vs 81.6%; p=0.005) and RF/ACPA seropositivity was associated with a better response (p=0.002). There were no new safety signals. Conclusions In this first prospective, international, non-interventional research evaluating the long-term IV abatacept retention, RF and ACPA seropositivity were predictors of 2-yr higher retention and better outcomes. Higher retention rates may be achievable with earlier vs later initiation of abatacept treatment, consistent with prior findings from a pooled analysis of EU and Canadian registries.1 References Iannone F et al. Clin Rheumatol (2016): doi:10.1007/s10067–016–3505–5. Disclosure of Interest R. Alten Grant/research support from: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, H.-M. Lorenz Consultant for: AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, SOBI, Medac, Novartis, Janssen-Cilag, AstraZeneca, Pfizer, Actelion, X. Mariette Grant/research support from: Biogen, Pfizer, UCB, Consultant for: Bristol-Myers Squibb, LFB, Pfizer, GSK, UCB, H. Nüßlein Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, M. Galeazzi: None declared, F. Navarro Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, Roche, Consultant for: Pfizer, MSD, Roche, UCB, AbbVie, Bristol-Myers Squibb, Jansen, Lilly, Speakers bureau: Pfizer, MSD, Roche, UCB, AbbVie, Bristol-Myers Squibb, M. Chartier Employee of: Bristol-Myers Squibb, Y. Elbez: None declared, C. Rauch Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Le Bars Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

AB0412 Less than 5% of real-life patients who switch from iv to sc abatacept in real-world clinical practice subsequently switch back to the iv formulation

Background Patients (pts) with RA may be able to switch from IV to SC abatacept with no loss of efficacy or safety concerns, but data are inconclusive.1–4 In the ACTION (AbataCepT In rOutiNe clinical practice; NCT02109666) study, a 1-year interim analysis showed that switching had no adverse clinical effect.5 Objectives To examine treatment patterns and explore abatacept formulation switching over 2 years in ACTION. Methods ACTION is a 2-year, prospective, observational study of pts with moderate-to-severe RA who initiated IV abatacept in Europe and Canada between May 2008 and December 2013. Assessments in biologic-naïve and biologic-failure pts were: baseline characteristics, rates of and reasons for switching (IV to SC), and re-switching to IV over 2 years. Descriptive data were generated: mean (SD) for continuous variables and n (%) for categorical variables. Rates of switching were estimated by Kaplan–Meier analysis. Cohorts were pooled to analyse further pts who switched owing to low numbers. Results In the ACTION cohort, 2350/2364 pts (99.4%) were evaluable for this analysis (673 [28.6%] biologic naïve, 1677 [71.4%] biologic failure). A total of 729 (43.4%) biologic-failure pts had received 1, and 948 (56.6%) had received ≥2 previous biologics. Baseline characteristics in biologic-naïve and biologic-failure pts, respectively, were: mean (SD) age 59.9 (12.7) and 56.9 (12.5) years; RA duration 7.2 (8.22) and 12.1 (9.13) years; 496 (73.7%) and 1379 (82.2%) were women; 621 (92.3%) and 1552 (92.5%) had received prior MTX; and 533 (79.2%) and 1386 (82.6%) had received corticosteroids. Over 2 years, 195 pts switched from IV to SC abatacept (57 biologic naïve, 138 biologic failure; Fig.). Reasons for switching were available for 172 pts (51 biologic naïve, 121 biologic failure; some had >1 reason); biologic naïve/biologic failure: pt wish 54.9%/62.0%, physician choice 31.4%/19.8%, safety 5.9%/9.9%, remission/major improvement 3.9%/5.0%, poor compliance 0%/4.1%, lack of efficacy 2.0%/3.3%, surgery 2.0%/0.8%, weight adjustment 2.0%/0%, other 49.0%/36.4%. Only eight pts (2.6%) re-switched to IV abatacept (2 biologic naïve, 6 biologic failure). Reasons for re-switching were: pt wish (n=4), lack of efficacy (n=4), safety issue (n=1) and other (n=2). Conclusions Less than 5% of pts who switched formulation from IV to SC abatacept in real-world clinical practice re-switched to the IV formulation, suggesting that switching has no adverse clinical impact. A change in formulation was mainly due to pt wish, reflecting their involvement in decision-making. References Keystone EC, et al. Ann Rheum Dis 2012;71:857–61. Mueller R, et al. Arthritis Rheumatol 2015;67(Suppl. 10):651–52. Reggia R, et al. J Rheumatol 2015;42:193–5. Monti S, et al. J Rheumatol 2015;42:1993–4. Alten R, et al. Ann Rheum Dis 2016;75(Suppl. 2):202. Disclosure of Interest R. Alten Grant/research support from: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, H.-M. Lorenz Consultant for: AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, SOBI, Medac, Novartis, Janssen-Cilag, Astra-Zeneca, Pfizer, Actelion, X. Mariette Grant/research support from: Biogen, Pfizer, UCB, Consultant for: Bristol-Myers Squibb, LFB, Pfizer, GSK, UCB, H. Nüßlein Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, M. Galeazzi: None declared, F. Navarro Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, Roche, Consultant for: Pfizer, MSD, Roche, UCB, AbbVie, Bristol-Myers Squibb, Jansen, Lilly, Speakers bureau: Pfizer, MSD, Roche, UCB, AbbVie, Bristol-Myers Squibb, M. Chartier Employee of: Bristol-Myers Squibb, J. Heitzmann: None declared, C. Rauch Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Le Bars Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

AB0267 Treatment paradigms in real-world practice: biologic agent use prior to and after discontinuation of abatacept in the action study

Background ACTION is a 2-year, observational study of patients (pts) with moderate-to-severe RA who initiated IV abatacept (ABA) in Canada and Europe (NCT02109666). Objectives To determine pt biologic (b)DMARD use prior to initiation and after discontinuation of ABA overall and by treatment line in ACTION. Methods Pts with RA initiated IV ABA as first- or second-/further-line therapy. Biologic-naïve and biologic-failure pts were enrolled during three periods between May 2008 and December 2013. Pts could switch administration routes (IV to SC) during treatment. Crude retention rates (Kaplan–Meier) were compared by log-rank test. Results Of the 2364 pts enrolled, 2350 were evaluable for analysis: 673 (28.6%) were biologic naïve and 1677 (71.4%) biologic failures. Baseline characteristics differed: biologic-failure pts had longer RA duration, higher CRP levels and prevalence of radiographic erosions, and lower rates of chronic obstructive pulmonary disease and neoplasms vs biologic-naïve pts. Most biologic-failure pts (96.7%) had previously received ≥1 TNF inhibitor (TNFi): 48.7% had received 1 and 48.0% ≥2 TNFi; 56.6% had received ≥2 bDMARDs. The overall 2-year retention rate was 47.9% and was higher for biologic-naïve vs biologic-failure pts (54.5 vs 45.2%; p<0.001); the most common reasons for ABA discontinuation were inefficacy (61.4 vs 67.7%) and safety (21.3 vs 21.2%). In pts who discontinued ABA, 83.0% started a bDMARD ≤6 months after discontinuation (Table), most commonly ABA IV. Mean (SD) days from stopping ABA to starting a bDMARD was similar for biologic-naïve (93.4 [51.3]) and biologic-failure pts (93.6 [48.0]). Among pts who restarted ABA, 62 (80.5%) biologic-naïve and 158 (85.0%) biologic-failure pts were considered to have discontinued as the time from last dose was >84 (IV) or >28 (SC) days, and thus were no longer temporary discontinuations, as predefined in the protocol. Three pts discontinued for bad compliance, 3 for lack of efficacy, 3 for remission/major improvement, 12 for safety and 15 for surgery. A good/moderate EULAR response was achieved by 76.7% of pts at the last follow-up before ABA discontinuation and 58.3% at ABA restart; mean (SD) DAS28 (CRP) was 3.2 (1.1) and 3.8 (1.4), respectively. bDMARD ≤6 months after ABA discontinuation bDMARD prior to initial ABA treatment in pts who restarted ABA Biologic naïve Biologic failure Biologic failure n=186 n=526 n=186 None 35 (18.8) 86 (16.3) Abatacept 77 (41.4) 186 (35.4) – IV 71 (38.2) 170 (32.3) SC 6 (3.2) 16 (3.0) TNFi 41 (22.0) 74 (14.1) 181 (97.3) Adalimumab 10 (5.4) 12 (2.3) 108 (58.1) Etanercept 13 (7.0) 21 (4.0) 125 (67.2) Infliximab 7 (3.8) 13 (2.5) 55 (29.6) Certolizumab 7 (3.8) 17 (3.2) 5 (2.7) Golimumab 4 (2.2) 11 (2.1) 2 (1.1) Other bDMARD 33 (17.7) 180 (34.2) 51 (27.4) Anakinra 1 (0.5) 4 (0.8) 5 (2.7) Rituximab 6 (3.2) 58 (11.0) 30 (16.1) Tocilizumab 26 (14.0) 118 (22.4) 21 (11.3) Data are n (%) Conclusions Prior to abatacept treatment, over half of biologic-failure pts had received ≥2 bDMARDs and most had received a TNFi. After initial discontinuation (protocol defined), over one-third of pts restarted abatacept. Disclosure of Interest R. Alten Grant/research support from: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, H.-M. Lorenz Consultant for: AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, SOBI, Medac, Novartis, Janssen-Cilag, AstraZeneca, Pfizer, Actelion, Speakers bureau: AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, SOBI, Medac, Novartis, Janssen-Cilag, AstraZeneca, Pfizer, Actelion, X. Mariette Grant/research support from: Biogen, Pfizer, UCB, Consultant for: Bristol-Myers Squibb, LFB, Pfizer, GSK, UCB, H. Nüßlein Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, M. Galeazzi: None declared, F. Navarro Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, Roche, Consultant for: Pfizer, MSD, Roche, UCB, AbbVie, Bristol-Myers Squibb, Jansen, Lilly, Speakers bureau: Pfizer, MSD, Roche, UCB, AbbVie, Bristol-Myers Squibb, M. Chartier Employee of: Bristol-Myers Squibb, Y. Elbez: None declared, C. Rauch Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Le Bars Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

AB0371 Is Switching from IV To SC Abatacept Therapy Sustainable in The Real World? 1-Year Analysis of The Prospective, International Action Study

Background Open-label clinical trials have shown that patients with RA can switch from IV to SC abatacept therapy with no efficacy loss or safety concerns;1,2 however, findings from single-centre, real-world studies are unclear.3,4 Objectives To examine characteristics at baseline and before switching, and reasons for switching, in patients who switched from IV to SC abatacept in the real-world ACTION study. Methods ACTION is a 2-year, prospective, observational study of patients with moderate-to-severe RA who initiated IV abatacept across Europe and Canada. Enrolment periods: May 2008–Dec 2010 (biologic naïve or failed prior biologics); Sept 2010–Dec 2013 (biologic naïve); Oct 2011–Dec 2013 (failed prior biologics). This was an interim analysis of 1-year data. Assessments: baseline characteristics; reasons for switching; efficacy at the time of switch measured by EULAR response, DAS28 (ESR), DAS28 (CRP), CDAI and SDAI. Results 2364 patients were enrolled and 2350 were evaluable. A total of 91 patients (3.9%) switched from IV to SC abatacept during their first study year: 19 were biologic naïve and 72 had failed prior biologics at study entry. Compared with non-switchers, the switch group had numerically higher percentages of patients with BMI ≥35 kg/m2, ≥1 co-morbidity and ≥2 prior anti-TNF failures, and lower mean disease activity, at baseline. Most patients (62.6%) who switched did so after >6 months in the study (Figure). Reasons for switching from IV to SC abatacept were available for 86 patients (94.5%; some patients had >1 reason): patient wish (53.5%), physicians preference (24.4%), safety (9.3%), poor compliance (4.7%), efficacy (2.3%), remission (2.3%), surgery (1.2%) and other (16.3%). Only 3/91 (3.3%) patients re-switched to IV abatacept; reasons were: patient wish, safety, efficacy (1 patient each). Prior to switching to SC abatacept, 64% of patients had a good/moderate EULAR response. According to mean (SD) values, disease activity before switching was moderate: DAS28 (ESR) 3.85 (1.09), DAS28 (CRP) 3.46 (1.07), CDAI 12.49 (7.70) and SDAI 13.6 (8.13). Conclusions Few patients switched from IV to SC abatacept and most who did so switched after >6 months allowing them to first achieve stable disease activity. Switching from IV to SC abatacept was primarily driven by patient or physician preference for the SC formulation. The very low rate of return to IV (3.3%) suggests that switching from IV to SC abatacept had no adverse clinical impact. References Keystone EC, et al. Ann Rheum Dis 2012;71:857–61. Mueller R, et al. Arthritis Rheumatol 2015;67(Suppl. 10):651–52. [Abstract 449] Reggia R, et al. J Rheumatol 2015;42:193–5. Monti S, et al. J Rheumatol 2015;42:1993–4. Disclosure of Interest R. Alten Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, H. Nüßlein Consultant for: Bristol-Myers Squibb, AbbVie, Celgene, Chugai, UCB, Pfizer, MSD, Novartis, Roche, Speakers bureau: Bristol-Myers Squibb, AbbVie, Celgene, Chugai, UCB, Pfizer, MSD, Novartis, Roche, M. Galeazzi: None declared, H. M. Lorenz Consultant for: AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, Sobi, Medac, Novartis, Janssen-Cilag, AstraZeneca, Pfizer, Actelion, Speakers bureau: AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, Sobi, Medac, Novartis, Janssen-Cilag, AstraZeneca, Pfizer, Actelion, X. Mariette Grant/research support from: Biogen, GSK, Pfizer, Speakers bureau: Bristol-Myers Squibb, GSK, Pfizer, sanofi, UCB, A. Cantagrel Grant/research support from: UCB, Pfizer, Consultant for: AbbVie, Bristol-Myers Squibb, Chugai, Lilly, MSD, Novartis, Pfizer, Roche, M. Chartier Consultant for: Bristol-Myers Squibb, Y. Elbez Employee of: Bristol-Myers Squibb, C. Rauch Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Le Bars Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

Anti-IL1 therapy in patients with refractory FMF living inGermany

About 10-20% of patients with familial Mediterranean fever (FMF) show an inadequate response to colchicine. Patients with colchicine-resistant FMF with or without AA-Amyloidosis can be treated with Interleukin-1 (IL-1)-inhibiting drugs.

AB0477 Retention Rates and Clinical Outcomes in Cohorts of Patients (Biologic Naïve or Failed Prior Biologics) Treated with Intravenous Abatacept in a Real-World Setting: 6-Month Results from the Action Study

Background The real-world ACTION study has shown abatacept (ABA) to be an effective and well-tolerated treatment for patients (pts) with RA. Previously, we reported results from ACTION in a cohort of pts enrolled between 2008 and 2010.1 Here, 6-mth results in all pts enrolled in ACTION between 2008 and 2013 are presented. Objectives To assess retention rates and effectiveness of IV ABA over 6 mths for all pts in the ACTION study. Methods ACTION is a 2-yr, international, non-interventional cohort of pts with RA who initiated IV ABA in three distinct periods (line of treatment and participating countries varied by cohort owing to feasibility and access): Cohort A, May 2008 to December 2010 (biologic naïve or failed prior biologics [majority]), follow-up (FU) completed; Cohort B, September 2010 to December 2013 (biologic naïve only); and Cohort C, December 2011 to December 2013 (failed prior biologics), FU ongoing. Data from all cohorts were pooled, as pt baseline characteristics were comparable for each treatment line. ABA retention (and 95% CI) over 6 mths was estimated by Kaplan–Meier; pts were censored at the date of last available data. Safety is reported for all enrolled pts at a data cut-off of August 2014; incidence rates (IR) calculated based on pt exposure in FU. Results 2343 pts were evaluable (1131, 550 and 662 in Cohorts A, B and C, respectively); 672 (28.7%) pts were biologic naïve and 1671 (71.3%) had failed ≥1 prior biologic agent: 726/2343 (31.0%) failed 1 biologic and 945/2343 (40.3%) ≥2 biologics. Differences between biologic-naïve pts and pts who failed prior biologics included: mean age (59.9 vs 57.0 yrs), RA duration (7.2 vs 12.1 yrs), CRP (1.66 vs 2.12 mg/dL), HAQ-DI (1.37 vs 1.50), erosive disease (58.1 vs 71.7%), use of ABA as monotherapy (16.5 vs 25.4%), and median dose of concomitant corticosteroids (5.0 vs 7.5 mg/day). Retention rate decreased with increasing number of previous biologic treatments (Figure). Safety data represent 3371 pt-yrs of FU at data cut-off. There were 335 serious AEs in 174/2359 (7.4%) pts (56 discontinuations reported) and 22 deaths, including 2 due to opportunistic infections (Pneumocystis jiroveci; multi-organ failure including Candida infection). Serious infections occurred in 69 pts (IR: 2.05/100 pt-yrs) including 1 case of latent TB and 3 non-TB opportunistic infections (Cytomegalovirus, Candida and P. jiroveci). There were 21 pts with malignancies (2 were pre-existing; IR: 0.62/100 pt-yrs), 17 with serious cardiac disorders, 12 with serious vascular disorders and 19 with serious hypersensitivity reactions. Conclusions The findings of the real-world ACTION study are consistent with previous clinical experience and demonstrate the benefits and safety of IV abatacept in a large cohort of pts. These data confirm the trend of abatacept demonstrating improved retention and clinical outcomes when used in earlier lines of RA treatment. References Nüßlein HG, et al. BMC Musculoskelet Disord 2014;15:14. Disclosure of Interest R. Alten Grant/research support from: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, H. Nüßlein Consultant for: Bristol-Myers Squibb, Abbvie, Chugai, UCB, Wyeth, Pfizer, MSD, Novartis and Roche, Speakers bureau: Bristol-Myers Squibb, Abbvie, Chugai, UCB, Wyeth, Pfizer, MSD, Novartis and Roche, M. Galeazzi: None declared, H.-M. Lorenz Consultant for: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, X. Mariette Grant/research support from: Biogen, GSK, Pfizer, Speakers bureau: Bristol-Myers Squibb, GSK, Pfizer, sanofi, UCB, A. Cantagrel Grant/research support from: Pfizer, UCB, Roche, Chugai, Speakers bureau: Bristol-Myers Squibb, Pfizer, Chugai, Abbvie, Nordic-Pharma, Fabre, MSD, Novartis, M. Chartier Consultant for: Bristol-Myers Squibb, C. Poncet Consultant for: Bristol-Myers Squibb [full-time contractor], Employee of: DOCS, C. Rauch Employee of: Bristol-Myers Squibb, M. Le Bars Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb