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ObjectiveEarly treatment of patients with rheumatoid arthritis (RA) with combination treatment starting with methotrexate, sulfasalazine, hydroxychloroquine and prednisolone (FIN-RACo strategy) is superior to monotherapy. A study was undertaken to determine whether infliximab (INFL) added to intensified FIN-RACo treatment for the initial 6 months improves the 2-year outcome.Methods99 patients with early untreated active RA were enrolled in an investigator-initiated, randomised, double-blind, multicentre, parallel-group trial. Primary outcomes were remission and radiological changes at 2 years. All patients started with FIN-RACo. In addition, they were randomised to receive INFL or placebo (Pla) from weeks 4 to 26.ResultsAt 24 months, 66% and 53%, respectively, of the patients in the FIN-RACo+INFL and FIN-RACo+Pla groups were in remission according to the modified American College of Rheumatology (ACR) criteria (p=0.19), 26% and 10% were in sustained modified ACR remission (p=0.042) and 82% in both groups were in remission by 28-joint disease activity score (not significant). Mean changes in the total Sharp-van der Heijde score were 0.2 and 1.4, respectively (p=0.0058).ConclusionsMost patients with early active RA achieve clinical remission and develop negligible joint damage with the intensified FIN-RACo regimen. Adding INFL for the first 6 months delays radiological progression.

Objective: To assess the intra-reader and inter-reader reliabilities of interpreting ultrasonography by several experts using video clips. Method: 99 video clips of healthy and rheumatic joints were recorded and delivered to 17 physician sonographers in two rounds. The intra-reader and inter-reader reliabilities of interpreting the ultrasound results were calculated using a dichotomous system (normal/abnormal) and a graded semiquantitative scoring system. Results: The video reading method worked well. 70% of the readers could classify at least 70% of the cases correctly as normal or abnormal. The distribution of readers answering correctly was wide. The most difficult joints to assess were the elbow, wrist, metacarpophalangeal (MCP) and knee joints. The intra-reader and inter-reader agreements on interpreting dynamic ultrasound images as normal or abnormal, as well as detecting and scoring a Doppler signal were moderate to good (κ = 0.52–0.82). Conclusions: Dynamic image assessment (video clips) can be used as an alternative method in ultrasonography reliability studies. The intra-reader and inter-reader reliabilities of ultrasonography in dynamic image reading are acceptable, but more definitions and training are needed to improve sonographic reproducibility.

Background Intra-articular glucocorticoid injections are recommended for local treatment of synovitis regardless of the disease severity or the concurrent therapy [1]. However, the accurate placement of the puncture is challenging and if not succeeded it may impair clinical outcome or even lead to complications. The accuracy rate of non-guided injections varies around 30% - 80% [2, 3] which emphasizes the need for needle guidance. In addition to established methods (e.g. ultrasound), electrical tissue properties can be utilized for needle guidance [4]. Objectives This study introduces a new real-time needle guidance method which utilizes bioimpedance spectroscopy (BIS) with standard 22G and 24G needles. In this exploratory clinical study the system parameters are tuned and performance tested. Methods The measurement system (Injeq Ltd) consisted of a conventional injection needle together with a bioimpedance probe (BIP) stylet connected to the measurement device (as shown in Figure). It performs bipolar BIS between the electrode at the tip of the stylet and the surrounding needle. Based on the BIS results, system classifies the tissue using mathematical model in real-time and beeps when synovial fluid is detected. Parameter tuning was performed during studies based on offline analysis. In this phase, 23 patients suffering from arthritis were injected to 31 joints by experienced rheumatologists. Success of the injection was verified by aspiration of synovial fluid, absence of resistance during injection and/or using ultrasound imaging for locating the needle. Results The electrical properties of human synovial fluid differ significantly from surrounding tissues. Small and inflamed joints do not appear to contain pure well conducting synovial fluid, but they are still distinguishable from the surrounding tissues. This kind of new class, termed Complex, was included to the model after 10 injections. After the inclusion, the device correctly detected either Complex or Pure synovial fluid in 18 out of 21 injections. One joint was dry and device provided true negative result. Remaining two injections were false negative. Conclusions BIP needle is a new, easy to use method for assisting placement of the needle during intra-articular injection. In this exploratory phase, synovial fluid detection functioned properly in 19/21 cases. Thus, BIP showed ability to provide needle guidance and the study will be continued to statistically significant phase. References Beukelman T et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care & Research 63.4 (2011): 465-482. Balint PV et al. Ultrasound guided versus conventional joint and soft tissue fluid aspiration in rheumatology practice: a pilot study. J. Rheumatol. 29.10 (2002): 2209-2213. Pichler W et al. Frequency of successful intra-articular puncture of finger joints: influence of puncture position and physician experience. Rheumatology 47.10 (2008): 1503-1505. Kalvoy H et al. Impedance-based tissue discrimination for needle guidance. Physiological measurement 30.2 (2009): 129-140. Disclosure of Interest P. Parmanne: None declared, E. Kankaanpaa: None declared, S. Maki Employee of: Injeq, J. Kari Employee of: Injeq, H. Relas: None declared, R. Tuompo: None declared, R. Peltomaa: None declared, K. Kronstrom Shareholder of: Injeq, Employee of: Injeq, R. Luosujarvi: None declared

Background Resistin is an adipocytokine related to insulin resistance, inflammation and arthritis (1). Objectives We investigated if resistin is associated with the disease activity and inflammation in DMARD-naive rheumatoid arthritis (RA) patients, if it possesses predictive value on the disease progression, and if TNFα is involved in these effects. Methods Ninety patients with early, DMARD-naive RA participated in the NEO-RACo study. The patients were treated for the first four weeks with a combination of methotrexate (max 25 mg/week), sulfasalazine (max 2 g/day), hydroxychloroquine (35 mg/kg/week), and prednisolone (7.5 mg/day) (FIN-RACo treatment strategy). Thereafter patients were randomized to receive either infliximab or placebo added on the combination therapy and infusions were given at weeks 4, 6, 10, 18 and 26. Patients were followed for 5 years. Human macrophage cell-line THP-1 was used to study the effects of resistin on TNFα production in the in vitro studies. Results At baseline, resistin levels correlated with disease activity and inflammation measured as DAS28 and ESR: when the patients were divided in tertiles based on their plasma resistin levels at baseline, DAS score showed positive linearity (p for linearity =0.0072) and similarly, ESR levels increased linearly in resistin tertiles (p for linearity The predictive value of baseline resistin was evaluated on the disease progression during the 5 years follow-up. Highest resistin predicted more rapid radiological progression in the FIN-RACo + placebo group as measured by change in Sharp-van der Heijde total score (Fig. 1A). However, the baseline resistin level was not predictive in relation to the remission rate. Interestingly, adding infliximab to the treatment delayed the radiological progression and there was no difference in the radiological progression in the FIN-RACo + infliximab group between the resistin tertiles (Fig. 1B). Resistin also increased TNFα production THP-1 macrophages in vitro. Conclusions High resistin level at the baseline was linked to active inflammatory disease and predicted erosive disease progression. Further, resistin increased the production of TNFα in macrophages in the in vitro studies and infliximab treatment overcame the poor predictive value of high resistin levels in the NEO-RACo study suggesting that the effects of resistin are mediated by TNFα. High resistin concentration may be a useful marker to distinguish patients with risk for erosive disease, who respond better to treatment with a combination of DMARDs and TNFα-antagonists rather than with traditional DMARDs only. References M. Scotece, J. Conde, K. Vuolteenaho, A. Koskinen, V. Lόpez, J. Gόmez-Reino, F. Lago, E. Moilanen, O. Gualillo. Adipokines as drug targets in joint and bone disease. Drug Discov Today, in press 2014. Acknowledgements The participating patients, research personnel and other members of NEO-RACo Study Group are greatly acknowledged. Disclosure of Interest K. Vuolteenaho Consultant for: *, H. Kautiainen Consultant for: *, T. Mottonen Consultant for: *, P. Hannonen Consultant for: *, M. Korpela Consultant for: *, M. Kauppi Consultant for: *, O. Kaipiainen-Seppanen Consultant for: *, R. Luosujarvi Consultant for: *, R. Nieminen Consultant for: *, M. Leirisalo-Repo Consultant for: *, E. Moilanen Consultant for: *All authors have received consulting fees or honoraria from all or some of the following: Abbott, Actelion, Amgen, Astra-Zeneca, BMS, Ely Lilly, GSK, MSD, Mundipharma, Pfizer, Roche, Schering-Plough, Servier, UCB Pharma. DOI 10.1136/annrheumdis-2014-eular.1680

Background Given the existing evidence that the degree of response to certolizumab pegol (CZP) at Week 12 is determinant of the probability of long-term response to CZP, a risk-sharing scheme (RSS) was created and embedded in a clinical decision rationale. It also aligns with recent European treatment guidelines, emphasizing a treat-to-target approach in rheumatoid arthritis (RA) with an intensive monitoring of patients and rapid, pro-active switching in case of non-response. Objectives Assessment of an RSS for CZP in terms of treatment response, per-patient value-for-money and affordability in the Finnish population. Methods To evaluate the effects and costs (administration, drug, in-patient, monitoring, adverse events, travelling, productivity; 2011 real value) of biologic treatments for RA in anti-TNF-naive patients, a literature search of American College of Rheumatology (ACR) ACR70, ACR50 and ACR20 outcomes at weeks 12 and 24, and Bayesian network meta-analyses were carried out. Per-patient cost-effectiveness and per-population budget impact were assessed in a new, hybrid stochastic Markov model, combining cost-effectiveness and budget impact analyses. Using 12-week cycles, multiple comparators (so-called treatment-mix modelling, ie. in proportion to their current market share in Finland) and a Finnish societal perspective that includes direct and indirect costs, anti-TNF therapies were compared over a 5-year horizon. If an ACR20 response was achieved at Week 12, CZP treatment was continued. Otherwise, CZP acquisition costs were refunded under a proposed RSS, and alternative treatment was initiated. Quality-adjusted life-years were estimated based on a relationship between EQ-5D and Health Assessment Questionnaire. The budget impact part assumes a rising incidence of RA during 2013–2017 in Finland and includes treatment persistence estimates. Results The meta-analysis showed that 72.4% (95% confidence interval 64.7–80.3%) of CZP-treated patients had an ACR20 response at Week 12, compared to estimated ACR20 response at Week 12 of 60.2% with adalimumab, 52.5% with etanercept, and 55.5% with golimumab. Over the 5 years, introducing the CZP RSS for all new patients provided cost savings per patient of €4,796 together with 0.04 additional quality-adjusted life-years (with 100% cost-effectiveness probability). If using an RSS, approximately 4.7% of CZP acquisition costs would be refunded. The correspondent budget per patient-year was estimated at €27,310 under the current mix of anti-TNFs and subsequent therapies, which could be reduced to average €26,178 per patient-year if all starting patients were to receive CZP with RSS. Whereas the magnitude of the budget impact varied according to different assumptions, all the sensitivity analyses conducted were consistent and showed that CZP would reduce costs and improve patient health. Conclusions The current analysis showed that CZP is effective and cost-effective compared to the current mix of treatments in Finland. An outcomes-based RSS would increase affordability even further. Acknowledgements The authors acknowledge Costello Medical Consulting for editorial assistance which was funded by UCB Pharma. Disclosure of Interest C. Asseburg Employee of: ESiOR Oy, E. Soini Shareholder of: ESiOR Oy, Grant/research support from: ISPOR, Kauneuskeskus Mona Oy, University of Eastern Finland, Consultant for: Kauneuskeskus Mona Oy, Employee of: ESiOR Oy, Paid instructor for: Kauneuskeskus Mona Oy, Speakers bureau: University of Eastern Finland, Kuopio University Hospital, K. Puolakka Consultant for: Pfizer, MSD, UCB Pharma, O. Purcaru Employee of: UCB Pharma, M. Taiha Employee of: UCB Pharma, R. Luosujarvi Speakers bureau: BMS, Abbott, Pfizer, RiLu