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Objectives To investigate the effect of tumor necrosis factor inhibitor (TNFi) initiation on working ability and health care resource utilization among axial spondyloarthritis patients in a real-life setting. Methods Patients with a clinical diagnosis of non-radiographic (nr-axSpA) or radiographic axial spondyloarthritis initiating their first TNFi were identified from the ROB-FIN registry. Sickness absences, including sick leaves and disability pensions, in- and outpatient days and rehabilitation rates one year before and after initiating the medication were retrieved from national registries. Factors affecting result variables were studied using multivariate regression analysis. Results Overall, 787 patients were identified. Rates of work disability days per year were 55.6 the year before treatment onset and 55.2 the year after, with significant differences between patient subgroups. The rate of sick leaves decreased after starting TNFi treatment. However, the rate of disability pensions continued to rise. Patients with the diagnosis of non-radiographic axial spondyloarthritis experienced decrease in overall work disability and especially fewer sick leaves. No gender differences were detected. Conclusions The TNFis interrupt the increase in work disabled days evident during the year prior to their initiation. However, the overall work disability remains high. Treating patients earlier in the nr-axSpA phase regardless of gender appears important in maintaining work ability. Lay summary What does this mean for patients? Maintaining patients’ ability to work is a complex and challenging task that deserves special attention when treating people with chronic inflammatory diseases, such as ankylosing spondylitis and non-radiographic spondyloarthritis (nr-axSpA). Work disability remains a problem among these patients despite the evolving treatment options. We investigated how a type of drug called tumour necrosis factor inhibitor (TNFi) affects working ability in people with nr-axSpA in a real-life setting in Finland. We used data on patients and their treatment from a database called the National Register for Antirheumatic and Biologic Treatment in Finland. We compared data on sick leave, in- and outpatient days and rehabilitation one year before and after starting TNFi medication. Our results show that TNFi medication substantially reduces the amount of sick leave patients need to take, especially for people with nr-axSpA. However, we found that the amount of disability pension claimed rises steadily despite patients starting TNFi medication. Taking these results together, we conclude that starting TNFi medication may interrupt nr-axSpA patients’ decline in work ability. However, effective ways of maintaining patients’ ability to work are still needed.

Objective: To compare incidences of neuroinflammatory events, including demyelinating disease (DML), inflammatory polyneuropathies (IPN) and multiple sclerosis (MS), in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA; including psoriatic arthritis) starting a tumour necrosis factor inhibitor (TNFi), investigating whether monoclonal TNFi antibodies (other TNFis (oTNFis)) confer higher risk than etanercept.Methods: This is an observational cohort study including patients from the five Nordic countries starting a TNFi in 2001-2020. Time to first neuroinflammatory event was identified through register linkages. We calculated crude incidence rates (cIR) per 1000 person-years and used multivariable-adjusted Cox regression to compare incidences of neuroinflammatory events overall and for DML, IPN and MS with oTNFi versus etanercept. We further examined individual TNFis and indications.Results: 33 883 patients with RA and 28 772 patients with SpA were included, initiating 52 704 and 46 572 treatment courses, respectively. In RA, we observed 135 neuroinflammatory events (65% DML) with cIR of 0.38 with oTNFi and 0.34 with etanercept. The HR of oTNFi versus etanercept was 1.07 (95% CI 0.74 to 1.54) for any neuroinflammatory event, 0.79 (95% CI 0.51 to 1.22) for DML, 2.20 (95% CI 1.05 to 4.63) for IPN and 0.73 (95% CI 0.34 to 1.56) for MS. In SpA, we observed 179 events (78% DML) with cIR of 0.68 with oTNFi and 0.65 with etanercept. The HR for any neuroinflammatory event, DML, IPN and MS was 1.06 (95% CI 0.75 to 1.50), 1.01 (95% CI 0.68 to 1.50), 1.28 (95% CI 0.61 to 2.69) and 0.94 (95% CI0.53 to 1.69), respectively.Conclusion: The cIRs of neuroinflammatory events are higher in SpA than in RA, but the choice of specific TNFi does not seem to play an important role in the risk of neuroinflammatory events. Objective To compare incidences of neuroinflammatory events, including demyelinating disease (DML), inflammatory polyneuropathies (IPN) and multiple sclerosis (MS), in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA; including psoriatic arthritis) starting a tumour necrosis factor inhibitor (TNFi), investigating whether monoclonal TNFi antibodies (other TNFis (oTNFis)) confer higher risk than etanercept. Methods This is an observational cohort study including patients from the five Nordic countries starting a TNFi in 2001-2020. Time to first neuroinflammatory event was identified through register linkages. We calculated crude incidence rates (cIR) per 1000 person-years and used multivariable-adjusted Cox regression to compare incidences of neuroinflammatory events overall and for DML, IPN and MS with oTNFi versus etanercept. We further examined individual TNFis and indications. Results 33 883 patients with RA and 28 772 patients with SpA were included, initiating 52 704 and 46 572 treatment courses, respectively. In RA, we observed 135 neuroinflammatory events (65% DML) with cIR of 0.38 with oTNFi and 0.34 with etanercept. The HR of oTNFi versus etanercept was 1.07 (95% CI 0.74 to 1.54) for any neuroinflammatory event, 0.79 (95% CI 0.51 to 1.22) for DML, 2.20 (95% CI 1.05 to 4.63) for IPN and 0.73 (95% CI 0.34 to 1.56) for MS. In SpA, we observed 179 events (78% DML) with cIR of 0.68 with oTNFi and 0.65 with etanercept. The HR for any neuroinflammatory event, DML, IPN and MS was 1.06 (95% CI 0.75 to 1.50), 1.01 (95% CI 0.68 to 1.50), 1.28 (95% CI 0.61 to 2.69) and 0.94 (95% CI0.53 to 1.69), respectively. Conclusion The cIRs of neuroinflammatory events are higher in SpA than in RA, but the choice of specific TNFi does not seem to play an important role in the risk of neuroinflammatory events.

ObjectivesTo evaluate the risk of haematological malignancies in patients with psoriatic arthritis (PsA) overall, and in relation to treatment with tumour necrosis factor inhibitors (TNFi).MethodsWe identified that patients with PsA starting a first TNFi from the clinical rheumatology registers (CRR) in the five Nordic countries (n=10 621) and biologics-naïve PsA patients from (1) the CRR (n=18 705) and (2) the national patient registers (NPR, n=27 286, Sweden and Denmark) from 2006 through 2019. For Sweden and Denmark, general population comparators were matched 5:1 to PsA patients on birth year, year at start of follow-up and sex. By linkage to the national cancer registers in all countries, we collected information on haematological malignancies overall, and categorised into lymphoid or myeloid types. We estimated incidence rate ratios (IRRs) with 95% CIs using modified Poisson regression for TNFi-treated versus biologics-naïve PsA patients and versus the general population adjusted for age, sex, calendar period and country.ResultsDuring 59 827 person-years, 40 haematological malignancies occurred among TNFi-treated patients with PsA resulting in a pooled IRR of 0.96 (0.68–1.35) versus biologics-naïve PsA from CRR and an IRR of 0.84 (0.64–1.10) versus biologics-naïve PsA from NPR. The IRR of haematological malignancies in PsA overall versus general population comparators was 1.35 (1.17–1.55). The estimates were largely similar for lymphoid and myeloid malignancies.ConclusionsTreatment with TNFi in patients with PsA was not associated with an increased incidence of haematological malignancies. Conversely, a moderately increased underlying risk was seen in patients with PsA compared with the general population.

Objectives In axial spondyloarthritis (axSpA), switching between multiple biologic or targeted synthetic (b/ts-) DMARDs might indicate difficult-to-treat disease. We aimed to explore the occurrence of multiple switching in routine care axSpA patients using various definitions, and to identify associated clinical characteristics upon start of first b/tsDMARD (baseline). Methods Observational cohort study including patients with axSpA starting a first-ever b/tsDMARD 2009–2018 based on data from five biologic registries (Denmark/Sweden/Finland/Norway/Iceland). Comorbidities and extra-articular manifestations were identified through linkage to national registries. Multi-switching was defined in overlapping categories according to b/tsDMARD treatment history: treatment with ≥3, ≥4 or ≥5 b/tsDMARDs during follow-up. We explored the cumulative incidence of patients becoming multi-switchers with ≥3 b/tsDMARDs stratified by calendar-period (2009–2011, 2012–2013, 2014–2015, 2016–2018). In the subgroup of patients starting a first b/tsDMARD 2009–2015, baseline characteristics associated with multi-switching (within 3 years’ follow-up) were explored using multiple logistic regression analyses. Results Among 8398 patients included, 6056 patients (63% male, median age 42 years) started a first b/tsDMARD in 2009–2015, whereof proportions treated with ≥3, ≥4 or ≥5 b/tsDMARDs within 3 years’ follow-up were 8%, 3% and 1%, respectively. Calendar-period did not affect the cumulative incidence of multi-switching. Baseline characteristics associated with multi-switching (≥3 b/tsDMARDs) were female gender, shorter disease duration, higher patient global score, comorbidities and having psoriasis but not uveitis. Conclusion In this large Nordic observational cohort of axSpA patients, multiple switching was frequent with no apparent time-trend. Clinical associated factors included gender, but also previous comorbidities and extra-articular manifestations illustrating the ongoing challenge of treating this patient group.

ObjectiveIn rheumatoid arthritis (RA), evidence regarding the effectiveness of a second biologic disease-modifying antirheumatic drug (bDMARD) in patients whose first-ever bDMARD was a non–tumor necrosis factor inhibitor (TNFi) bDMARD is limited. The objective of this study was therefore to assess the outcome of a second bDMARD (non-TNFi: rituximab [RTX], abatacept [ABA], or tocilizumab [TCZ], separately; and TNFi) after failure of a non-TNFi bDMARD as first bDMARD.MethodsWe identified patients with RA from the 5 Nordic biologics registers who started treatment with a non-TNFi as first-ever bDMARD but switched to a second bDMARD. For the second bDMARD, we assessed drug survival (at 6 and 12 months) and primary response (at 6 months).ResultsWe included 620 patients starting a second bDMARD (ABA 86, RTX 40, TCZ 67, and TNFi 427) following failure of a first non-TNFi bDMARD. At 6 and 12 months after start of their second bDMARD, approximately 70% and 60%, respectively, remained on treatment, and at 6 months, less than one-third of patients were still on their second bDMARD and had reached low disease activity or remission according to the Disease Activity Score in 28 joints. For those patients whose second bMDARD was a TNFi, the corresponding proportion was slightly higher (40%).ConclusionThe drug survival and primary response of a second bDMARD in patients with RA switching due to failure of a non-TNFi bDMARD as first bDMARD is modest. Some patients may benefit from TNFi when used after failure of a non-TNFi as first bDMARD.

Objectives To investigate whether TNF inhibitors (TNFi) are associated with increased risk of solid cancer in patients with psoriatic arthritis (PsA). Methods From the Nordic clinical rheumatology registers (CRR) here: SRQ/ARTIS (Sweden), DANBIO (Denmark), NOR-DMARD (Norway), ROB-FIN (Finland) and ICEBIO (Iceland) we identified PsA patients who started a first TNFi 2001–2017 (n = 9655). We identified patients with PsA not treated with biologics from (i) the CRR (n = 14 809) and (ii) the national patient registers (PR, n = 31 350). By linkage to the national cancer registers, we collected information on incident solid cancer overall and for eight cancer types. We used Cox regression to estimate hazard ratio (HR) with 95% CI of cancer (per country and pooled) in TNFi-exposed vs biologics-naïve, adjusting for age, sex, calendar period, comorbidities and disease activity. We also assessed standardized incidence ratios (SIR) in TNFi-exposed PsA vs the general population (GP). Results We identified 296 solid cancers among the TNFi-exposed PsA patients (55 850 person-years); the pooled adjusted HR for solid cancer overall was 1.0 (0.9–1.2) for TNFi-exposed vs biologics-naïve PsA from the CRR, and 0.8 (0.7–1.0) vs biologics-naïve PsA from the PRs. There were no significantly increased risks for any of the cancer types under study. The pooled SIR of solid cancer overall in TNFi treated PsA vs GP was 1.0 (0.9–1.1). Conclusion In this large cohort study from five Nordic countries, we found no increased risk of solid cancer in TNFi-treated PsA patients, neither for solid cancer overall nor for eight common cancer types.

Objective: To describe baseline characteristics and to compare treatment effectiveness of secukinumab versus tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA) using adalimumab as the main comparator. Methods: This was an observational, prospective cohort study. Patients with SpA (clinical ankylosing spondylitis, nonradiographic axial SpA, or undifferentiated SpA) starting secukinumab or a TNFi during 2015–2018 were identified from 5 Nordic clinical rheumatology registries. Data on comorbidities and extraarticular manifestations (psoriasis, uveitis, and inflammatory bowel disease) were captured from national registries (data available in 94% of patients) and included in multivariable analyses. We assessed 1-year treatment retention (crude survival curves, adjusted hazard ratios [HRadj] for treatment discontinuation) and 6-month response rates (Ankylosing Spondylitis Disease Activity Score [ASDAS] score adj 1.43 [95% CI 1.12–1.81]). Across treatment lines, secukinumab had poorer estimates for 6-month response rates than adalimumab, statistically significantly only for the third-plus line (adjusted analyses: ASDAS score

Publisher's version (útgefin grein), [No abstract available], This study was partly funded by grants from Nord-Forsk and FOREUM.

Objectives To assess secular trends in baseline characteristics of PsA patients initiating their first or subsequent biologic DMARD (bDMARD) therapy and to explore prescription patterns and treatment rates of bDMARDs from 2006 to 2017 in the Nordic countries. Methods PsA patients registered in the Nordic rheumatology registries initiating any treatment with bDMARDs were identified. The bDMARDs were grouped as original TNF inhibitor [TNFi; adalimumab (ADA), etanercept (ETN) and infliximab (IFX)]; certolizumab pegol (CZP) and golimumab (GOL); biosimilars and ustekinumab, based on the date of release. Baseline characteristics were compared for the five countries, supplemented by secular trends with R2 calculations and point prevalence of bDMARD treatment. Results A total of 18 089 patients were identified (Denmark, 4361; Iceland, 449; Norway, 1948; Finland, 1069; Sweden, 10 262). A total of 54% of the patients were female, 34.3% of patients initiated an original TNFi, 8% CZP and GOL, 7.5% biosimilars and 0.3% ustekinumab as a first-line bDMARD. Subsequent bDMARDs were 25.2% original TNFi, 9% CZP and GOL, 12% biosimilars and 2.1% ustekinumab. From 2015 through 2017 there was a rapid uptake of biosimilars. The total of first-line bDMARD initiators with lower disease activity increased from 2006 to 2017, where an R2 close to 1 showed a strong association. Conclusion Across the Nordic countries, the number of prescribed bDMARDs increased from 2006 to 2017, indicating a previously unmet need for bDMARDs in the PsA population. In recent years, PsA patients have initiated bDMARDs with lower disease activity compared with previous years, suggesting that bDMARDs are initiated in patients with a less active inflammatory phenotype.

Background:Interstitial lung disease (ILD) is an established extra-articular manifestation of rheumatoid arthritis (RA). Few studies have investigated the prevalence of ILD in patients with psoriatic arthritis (PsA). Methotrexate (MTX) is frequently used in the treatment of both RA and PsA and has been suggested to be a risk factor for the development of ILD. It is of interest to understand the interaction between disease and treatment in the development of ILD.Objectives:To compare the incidence of ILD between patient with PsA and RA treated with biologic disease modifying antirheumatic drugs (bDMARDS), with or without MTX as a co-medication.Methods:Cohorts of patients with RA and PsA starting bDMARD were identified in Nordic registers (Danish nationwide clinical register for patients with RA (DANBIO), Register on antirheumatic and biological therapy in Finland (ROB-FIN), Icelandic nationwide database of biologic therapy (ICEBIO), Norwegian Antirheumatic Drug Register (NOR-DMARD), and the Swedish Rheumatology Quality Register (SRQ)). Linkages to the National Patient Registers and to the Cause of Death Registers were performed in each country to identify cases of ILD. Each individual patient could contribute several treatment courses. ILD was identified as hospital or death certificate ICD10 codes of ILD (J84.1, J84.8, J84.9, J70.2, J70.3, J70.4, J99.0, J99.1, J99.8) given during the follow-up period which was defined as the treatment course duration, plus a 30-day wash-out period added to the end of treatment course period. MTX co-medication was specified as use of MTX at the start of bDMARD. Incidence rates (IR) for any ILD were calculated per 1000 person years at risk (PYR) for each country. The five cohorts were pooled and incidence rate ratios (IRR) for PsA vs. RA were calculated. Hazard ratios (HR) for any ILD in PsA vs. RA were estimated in Cox regression models adjusted for age, gender and repeated observations, and stratified for the use of MTX co-medication.Results:Overall 47 987 individual patients representing 89 239 bDMARD treatment courses and contributing 201 279 PYR were included in the study (Table 1). Methotrexate was reported as comedication in 29 916 (33.5 %) of the treatment courses (PsA vs. RA, 30.4 % vs 34.5 %). 970 cases of ILD were identified during the follow-up period. The risk of ILD was consistently lower in patients with PsA compared to patients with RA in all countries. In models stratified for co-medication the HR for ILD in PsA vs. RA was 0.34 (0.21-0.57) in patients treated with MTX and 0.26 (0.18-0.36) in patients not treated with MTX.Table 1.Interstitial lung disease in PsA vs. RA in five Nordic biologic registersDENMARKFINLANDICELANDNORWAYSWEDENRAPsARAPsARAPsARAPsARAPsANumber of individuals78293386494610916754701590999205966393Number of treatment courses17 07266408634184512808592379142738 27910 824Age baseline (SD)57.3 (13.1)49.0 (12.6)53.8 (13.4)48.8 (11.4)53.9 (14.2)50.1 (13.3)53.8 (13.7)48.7 (12.0)57.1 (13.7)50.6 (12.8)Female n (%)12 963 (76)3929 (59)6571 (76)933 (51)969 (76)551 (65)1815 (77)818 (57)29 635 (77)6162 (57)Number of PYR4023513986217984910451727994556265312033427412ILD-events within PYR2182213287232668028IR pr 1000 PYR5.41.66.11.61.50.77.02.35.71.0IRR PsA vs RA crude0.29 (0.18-0.45)0.27 (0.11-0.55)0.46 (0.05-2.42)0.32(0.11-0.78)0.18 (0.12-0.26)HR PsA vs RA0.31 (0.17-0.56)0.46 (0.22-0.96)0.62 (0.12-3.14)0.19 (0.06-0.54)0.25 (0.17-0.37)PYR: Patient years at risk, IR: Incidence rates, IRR: Incidence rate ratios, HR: Hazard RatiosConclusion:In these preliminary analyses, the incidence of ILD is lower in bDMARD treated PsA vs. RA patients, irrespective of co-medication with MTX. This indicates that the clinician should consider the rheumatological diagnosis when assessing the risk for future ILD in patients treated with bDMARDs and MTX.Acknowledgements:Partly funded by NordForsk and FOREUMDisclosure of Interests:Sella Aarrestad Provan Consultant of: Novartis, Grant/research support from: Boehringer-Ingelheim, Brigitte Michelsen: None declared, Lotta Ljung: None declared, Thorarinn Jonmundsson: None declared, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Daniela Di Giuseppe: None declared, Merete Lund Hetland Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis, Consultant of: Eli Lilly, Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Guðrún Björk Reynisdóttir: None declared, Bente Glintborg: None declared, Eirik kristianslund: None declared, Heikki Relas: None declared, Kalle Aaltonen: None declared, Dan Nordström Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, MSD, Novartis, Pfizer, Roche and UCB., Consultant of: Abbvie, BMS, Celgene, Eli Lilly, MSD, Novartis, Pfizer, Roche and UCB., Tore K. Kvien Speakers bureau: Amgen, Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz, Sanofi., Consultant of: AbbVie, Amgren, Biogen, Celltrion, Eli Lilly, Gilead, Mylan, Novartis, Pfizer, Roche, Sandoz, Sanofi., Johan Askling Grant/research support from: Abbvie, BMS, Eli Lilly, Merck, Pfizer, Roche, Samsung Bioepis, and Sanofi

Background:In clinical practice, some patients with axial spondyloarthritis (axSpA) fail several consecutive biological treatments (bDMARDs). How this group of ”refractory” patients should best be defined, how common they are, and what their characteristics are, is poorly understood.Objectives:To explore the point prevalence of bDMARD refractory disease in axSpA over time, according to different definitions, and to describe the characteristics of refractory vs. not-refractory patients upon start of their first bDMARD.Methods:Observational prospective cohort study. Patients with axSpA (ankylosing spondylitis/non-radiographic axial SpA) starting a first bDMARD 2009-2018 were identified in biologic registries in Denmark, Sweden, Finland, Norway and Iceland. Clinical characteristics and treatments were retrieved, and data were pooled for analysis.Refractory disease was defined based on the number of different bDMARD treatments started in individual patients: mild (≥3 bDMARDs), moderate (≥4), and strict (5 or more). Restart of same bDMARD with another bDMARD in between counted as separate courses whereas switch from originator to corresponding biosimilar was ignored.Proportions of patients fulfilling each definition of refractory disease at 2 and 5 years after the start of 1st bDMARD were calculated.Point-prevalence per calendar-year was calculated as the number of patients with refractory disease at the end of each year, divided by the total number of patients ever having starting a first bDMARD before that time-point, and who were still alive and resident in the country.Results:The point prevalence of refractory axSpA increased with calendar-time (Figure). Among 12,037 included axSpA patients (64% male), the point-prevalence of bDMARD refractory disease in 2018 was 16%/7%/3% according to mild/moderate/strict definitions (Table).Table 1.Biologic refractory axSpA according to three definitionsA.Baseline characteristics upon start 1st bDMARDRefractory definitionOverall cohortMILDMODERATESTRICTN120371969832351Age, years42 (13)41 (12)41 (12)41 (12)Male, %64%57%54%56%Disease duration, years7 (10)6 (9)6 (8)5 (8)BASDAI, 0-10053 (28)60 (29)63 (27)66 (35)ASDAS3.3 (1.1)3.5 (1.2)3.6 (1.0)3.7 (1.1)CRP, mg/L16 (23)18 (26)21 (28)23 (32)Patient global, VAS, 0-10059 (25)65 (22)66 (22)67 (23)Patient Pain, VAS, 0-10057 (24)62 (22)63 (22)63 (22)Fatigue, VAS, 0-10059 (27)66 (26)66 (26)68 (25)B.Proportions of patients having refractory disease 2 and 5 years after start of their first bDMARD2 years, %5%1%0%5 years, %13%4%1%Numbers are means (SD) unless otherwise statedUpon start of their 1st bDMARD, patients later fulfilling the definitions for refractory axSpA were more frequently women, had shorter disease duration, higher C-reactive protein and higher patient reported outcomes.Overall, 5%/1%/0% had mild/moderate/strict refractory disease 2 years after start of first bDMARD, after 5 years it was 13%/4%/1% (Table).Conclusion:In this large Nordic observational cohort of axSpA patients treated in routine care, we could demonstrate that a substantial proportion of all patients had used multiple bDMARDs. In 2018, one in six patients had received ≥3 bDMARDs, indicating a bDMARD refractory disease. Multiple switching was more frequent during later years, probably due to more bDMARDs becoming available. The characteristics of refractory axSpA, including sex and disease activity, will have to be further explored, as will the impact of refractory disease on long-term outcomes.Acknowledgements:the DANBIO, SRQ, ICEBIO, ROB-FIN and NOR-DMARD registries.Partly sponsored by Nordforsk and Foreum.Disclosure of Interests:Daniela Di Giuseppe: None declared, Ulf Lindström: None declared, Kalle Aaltonen: None declared, Heikki Relas Speakers bureau: Abbvie, Celgene, MSD, Roche, Sella Aarrestad Provan: None declared, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Merete L. Hetland Grant/research support from: AbbVie, Biogen, BMS, Celtrion, Eli Lilly Denmark A/S, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopis, Sandoz. MLH chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs the EuroSpA research collaboration, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary use of quality data and is partly funded by Novartis., Johan Askling: None declared, Tanja Schjødt Jørgensen: None declared, Lene Dreyer Speakers bureau: Eli-Lilly and Galderma, Grant/research support from: BMS, Dan Nordström: None declared, Brigitte Michelsen: None declared, Arni Jon Geirsson: None declared, Lennart T.H. Jacobsson: None declared, Bente Glintborg Grant/research support from: Abbvie, BMS, Pfizer, Lundbeck foundation

To assess what proportion of patients with disease-modifying anti-rheumatic drug (DMARD)-naïve early rheumatoid arthritis (ERA) reach 28-joint Disease Activity Score (DAS28) remission over 1 year, and remission variability across clinics in Finland.Patients with DMARD-naïve newly diagnosed inflammatory arthritis were recruited. The proportion of patients in 28-joint Disease Activity Score with three variables (DAS28-3) remission was compared across sites. Repeated measures were analysed using a mixed models approach with appropriate distribution and link function.In total, 611 patients were recruited at five sites: 67% were female; the mean (sd) age was 57 (16) years; 71% and 68% were positive for rheumatoid factor and anti-cyclic citrullinated peptides, respectively; and 23% had radiographic erosions. A total of 506 (83%) fulfilled the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for rheumatoid arthritis for further analyses. DAS28-3 remission was met by 68% and 75% at 3 and 12 months, respectively. The clinical site had no effect on remission when adjusted for confounders. At baseline, 68% used methotrexate-based combination therapy, and 31% used triple therapy with methotrexate, hydroxychloroquine, and sulphasalazine (the Fin-RACo regimen). In multivariate analysis, the only independent predictors of DAS28-3 remission at 12 months were lower baseline DAS28-3 and triple therapy as the initial treatment.Three out of four DMARD-naïve ERA patients in Finland are in remission during the first year from the diagnosis. High remission rates were achieved for most patients with the use of conventional synthetic DMARDs in combination. Treatment of DMARD-naïve ERA patients with the FIN-RACo regimen is a predictor of DAS28-3 remission in real-life rheumatology settings.

Background:Tumor necrosis factor inhibitors (TNFi) have been available for more than a decade for treatment of spondyloarthrtitis (SpA). Secukinumab (SEC) represents a new mode of action, but few studies have compared outcomes in patients(pts) treated with SEC vs TNFi – and the optimal treatment strategy in routine care remains to be established. Comparative studies between SEC and adalimumab (ADA) are ongoing.Objectives:To describe baseline characteristics and compare 1-yr treatment retention of SEC vs TNFi (ADA/certolizumab pegol(CLZ)/etanercept(ETN)/golimumab(GOL)/infliximab(IFX)) in SpA-pts from 5 Nordic countries.Methods:Observational, prospective cohort study. Pts with SpA (ankylosing spondylitis/non-radiographic axial SpA/undifferentiated SpA) starting SEC or any TNFi during 2015-2018 were identified in clinical rheumatology registries of the Nordic countries. Baseline characteristics were retrieved. Country-specific data were pooled. 1-yr treatment retention of SEC vs TNFi was assessed through crude survival probability curves, retention rates and adjusted Cox regression analyses (ADA reference). Analyses were stratified by line of bDMARD and TNFi type.Results:In total, 10692 treatment courses (834 SEC, 9858 TNFi) in 7952 patients were included. SEC was rarely used as 1stbDMARD (Table 1), whereas it was the drug most frequently used as 3rd+ line (Table 2). Baseline characteristics were numerically similar for SEC vs TNFi (Table 1).Table 1.Patient characteristics at treatment start1stline2ndline3rd+ lineSECTNFiSECTNFiSECTNFiN70518615626056082067Male, %535544534546Age, yrs45 (14)41 (14)45 (12)44 (13)47 (12)46 (13)BASDAI, mm45 (28)53 (22)52 (22)52 (24)63 (22)58 (24)Concomitant csDMARD, %182723232726Means (SD) unless otherwise statedTable 2.Table 2. 1-yr treatment retention (Kaplan Meier, Cox Regression)DrugRetentions rates, 1 yr % (95% CI)Adjusted* HR (95% CI) for discontinuation1stlineADA76 (73-79)1CLZ68 (63-72)1.4 (1.1-1.8)ETN74 (71-76)1.1 (0.9-1.3)GOL80 (77-84)0.8 (0.6-1.0)IFX65 (62-67)1.5 (1.3-1.8)SEC76 (62-85)0.9 (0.5-1.6)2ndlineADA72 (68-75)1CLZ58 (51-64)1.5 (1.2-1.9)ETN65 (61-68)1.2 (1.0-1.5)GOL73 (67-77)0.9 (0.7-1.2)IFX67 (63-71)1.2 (0.9-1.5)SEC67 (58-74)1.1 (0.8-1.5)3rd+ lineADA73 (68-77)1CLZ52 (46-57)2.0 (1.6-2.6)ETN65 (61-70)1.3 (1.0-1.6)GOL65 (60-70)1.3 (1.0-1.7)IFX61 (56-66)1.5 (1.2-1.9)SEC61 (57-65)1.4 (1.1-1.8)* by sex, baseline age, BASDAI, concomitant csDMARD (y/n/missing). Pts with missing baseline BASDAI (41-60%) excluded1-yr treatment retention varied between the TNFi (Figure,Table 2), with SEC showing retention rates comparable to ADA when used as 1stor 2ndline therapy. However, SEC retention was poorer than ADA when used as 3rd+ therapy, but comparable to retention of other TNFi.In adjusted Cox regression analyses, confidence intervals were wide and included 1 for SEC vs ADA (1st, 2ndline), whereas there was slightly poorer retention of SEC versus ADA when used as 3rd+ bDMARD (Table 2).Conclusion:These observational data in >10.000 biological treatment courses in SpA, showed that SEC was mainly used in bDMARD experienced pts. Baseline characteristics were similar in pts treated with SEC vs TNFi. The 1-yr retention for SEC was similar to that of the TNFi when used as 1stor 2ndline, but poorer than ADA regarding 3rd+ courses. Further analyses are planned to explore confounding by indication and channeling towards treatment.Acknowledgments:Glintborg/Lindström shared 1st author, Kristensten/Jacobsson shared last.Partly funded by NordForsk and FOREUMDisclosure of Interests:Bente Glintborg Grant/research support from: Grants from Pfizer, Biogen and Abbvie, Ulf Lindström: None declared, Daniela Di Giuseppe: None declared, Sella Aarrestad Provan Consultant of: Novartis, Björn Gudbjornsson Speakers bureau: Novartis and Amgen, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis, Brigitte Michelsen Grant/research support from: Research support from Novartis, Consultant of: Consulting fees Novartis, Johan K Wallman Consultant of: AbbVie, Celgene, Eli Lilly, Novartis and UCB Pharma, Kalle Aaltonen: None declared, Anna-Mari Hokkanen Grant/research support from: MSD, Tanja Schjødt Jørgensen Speakers bureau: Abbvie, Pfizer, Roche, Novartis, UCB, Biogen, and Eli Lilly, Rebekka L. Hansen: None declared, Arni Jon Geirsson: None declared, Kathrine L. Grøn Grant/research support from: BMS, Niels Steen Krogh: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma, Lars Erik Kristensen Consultant of: UCB Pharma (Advisory Board), Sannofi (Advisory Board), Abbvie (Advisory Board), Biogen (Advisory Board), Speakers bureau: AbbVie, Amgen, Biogen, Bristol-Myers Squibb,Celgene, Eli Lilly, Gilead, Forward Pharma, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, and UCB Pharma, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis and Pfizer

ObjectivesThe objective of this study was to evaluate the cost-effectiveness of abatacept, tocilizumab, and tumor necrosis factor (TNF) inhibitors as compared with rituximab in Finnish rheumatoid arthritis patients, who have previously been treated with TNF inhibitors.MethodsA patient-level simulation model was developed to predict costs and outcomes associated with four biological drugs (abatacept, tocilizumab, rituximab and TNF inhibitors) in the treatment of rheumatoid arthritis. Following lack of efficacy or adverse events, the patients were switched to another biological drug until all four options were exhausted. After that, the patients were assumed to receive a 6th line treatment until death. The patients' baseline characteristics and regression models used in the simulation were based on observational data from the National Register for Biological Treatments in Finland. Direct costs comprised drug costs, administration costs, costs of switching, and outpatient and inpatient care, while indirect costs included disability pension and sick leaves due to rheumatoid arthritis. Several subgroup and deterministic sensitivity analyses were conducted.ResultsDrug costs were the lowest for rituximab, but when administration costs and costs of switching were included, drug costs were the lowest for TNF inhibitors. Abatacept was associated with the highest drug costs, whereas rituximab was associated with the highest healthcare costs. In total, TNF inhibitors had the lowest direct costs, while rituximab had the highest direct costs. The amount of quality-adjusted life years (QALY) gained ranged from 9.405 for rituximab to 9.661 for TNF inhibitors. TNF inhibitors, abatacept, and tocilizumab were dominant in comparison to RTX.ConclusionsTNF inhibitors, abatacept, and tocilizumab had lower costs and higher QALYs than rituximab, and therefore, they were dominant in comparison to rituximab. As TNF inhibitors had the lowest costs and highest QALYs, they were the most cost-effective treatment option.

Background Psoriatic arthritis (PsA) is a chronic inflammatory disorder associated with skin and joint manifestations, several extra-articular symptoms, various comorbidities, and disability[1,2]. The emergence of tumour necrosis factor inhibitor (TNFi) therapy has dramatically changed the course of disease. Additional TNFi therapies (certolizumab pegol and golimumab) have been marketed, and recently ustekinumab has become available for PsA. Objectives To assess the use of biological agents (bDMARDs) in PsA from 2006-2017, using data from the Nordic Rheumatology registers. Methods Based on data from the registers DANBIO, ICEBIO, NOR-DMARD, ROB-FIN, and SRQ, PsA patients initiating bDMARDs or biosimilars, as a first or subsequent biological therapy were identified. Adalimumab, etanercept and infliximab were grouped as 1st generation therapies; certolizumab pegol, golimumab were grouped as 2nd generation therapies and biosimilar treatments were grouped. Treatments with ustekinumab were also identified. Pearson correlation tests were calculated and p>0.05 were considered significant. R2≈1 showed a strong correlation between the baseline characteristics. Results A total of 18,089 treatment initiations were identified (DANBIO 4,361, ICEBIO 449, NOR-DMARD 1,948, ROB-FIN 1,069, SRQ 10,262). 53.68% of the patients were female. Overall, 6,198 patients initiated 1st generation therapies, 1,447 2nd generation therapies, 1,353 biosimilars and 52 ustekinumab, as their first course of bDMARDs. Initiations of second or subsequent bDMARDs were 4,560, 1,630, 2,176 and 376 patients, respectively. The total of first course bDMARD initiators increased significantly from 2006-2017 (p Conclusion Across the Nordic countries the prescription pattern for biological therapies for PsA has changed significantly over time. The decreasing levels of both CRP scores and SJC suggest that PsA patients who initiate bDMARD treatment have changed towards a less active inflammatory phenotype from 2006-2017. Collaboration across registers will allow for robust assessment of the uptake of newer biological therapies. Overall the number of prescribed therapies increased during the observational period, indicating a previously unmet need for biological therapies in the Nordic population. References [1] Ballegaard C, Kristensen L. E, et al. Impact of comorbidities on tumour necrosis factor inhibitor therapy in psoriatic arthritis: a population-based cohort study. Arthritis. 2018;70(4):592-599. [2] Kristensen L. E, Jorgensen T. S, et al, Societal costs and patients’ experience of health inequities before and after diagnosis of psoriatic arthritis: a Danish cohort study. Ann Rheum Dis. 2017;(76):1495-1501. Acknowledgement This study was partly funded by a grant from NordForsk and FOREUM Disclosure of Interests Rebekka L. Hansen: None declared, Tanja Schjodt Jorgensen Consultant for: Abbvie, Roche, Novartis, UCB, Biogen, Eli Lilly., Speakers bureau: Abbvie, Roche, Novartis, UCB, Biogen, Eli Lilly., Lene Dreyer Consultant for: MSD, UCB and Janssen Pharmaceuticals, Speakers bureau: MSD, UCB and Janssen Pharmaceuticals, Speakers bureau: UCB, MSD, Eli Lilly and Janssen Pharmaceuticals., Bjorn Gudbjornsson: None declared, Johan Askling Grant/research support from: Karolinska Institutet (JA) has or has had research agreements with the following pharmaceutical companies, mainly in the context of the ATRIS national safety monitoring programme for rheumatology biologicals: Abbvie, BMS, MSD, Eli Lilly, Pfizer, Roche, Samsung Bioepis, and UCB., Consultant for: Karolinska Institutet has received remuneration for JA participating in ad boards arranged by Lilly, Novartis, and Pfizer., Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen, Pfizer, Consultant for: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck, Samsung Bioepis, Bente Glintborg Grant/research support from: Biogen, Pfizer, AbbVie, Daniela Di Giuseppe: None declared, Lennart T.H. Jacobsson Consultant for: LJ has received lecture and consulting fees from Pfizer, Abbvie, Novartis, Eli-Lily and Janssen, Tore K. Kvien Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB., Consultant for: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Oktal, Orion Pharma, Pfizer, Roche, Sandoz, Sanofi, Mylan and UCB, Speakers bureau: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Oktal, Orion Pharma, Pfizer, Roche, Sandoz, Sanofi and UCB, Dan Nordstrom Grant/research support from: MSD, Pfizer, Consultant for: AbbVie, BMS, MSD, Novartis, Roche, Pfizer, UCB, Speakers bureau: Novartis, UCB, Kalle Aaltonen: None declared, Sella Aarrestad Provan Consultant for: Novartis, Speakers bureau: Lilly, Eirik kristianslund: None declared, Johan K Wallman Consultant for: Consultant for AbbVie, Celgene, Eli Lilly, Novartis, and UCB Pharma., Thorvardur Jon Love Consultant for: Received reimbursment from Celgene for speaking about guidelines for the treatment of psoriatic arthritis, Lars Erik Kristensen Grant/research support from: UCB, Biogen, Janssen Pharmaceuticals, and Novartis, Consultant for: Consultant for AbbVie, Amgen, Biogen, BMS, Celgene, Eli Lilly, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB Pharma., Speakers bureau: Pfizer, AbbVie, Amgen, UCB, BMS, Biogen, MSD, Novartis, Eli Lilly and Company, and Janssen Pharmaceuticals

Background Tumour necrosis factor inhibitors (TNFi) effectively reduce inflammation in Psoriatic arthritis (PsA). However, a possible association between treatment with TNFi and an increased cancer risk has previously been suggested. Objectives To investigate the risk of cancer in TNFi treated PsA patients compared with standardized rates from the general population in Denmark, Finland, Iceland and Sweden. Methods TNFi-treated PsA patients were followed from first registration with TNFi-treatment in ARTIS (Sweden), DANBIO (Denmark), ICEBIO (Iceland) or ROB-FIN (Finland) and linked to the national Cancer Registry in each country. Patients with a cancer history prior to start of follow-up were excluded. We investigated the risk of primary cancer among TNFi-treated PsA patients compared with general population cancer rates standardized to age, sex and calendar period within each country. Standardized incidence ratios (SIRs) were estimated for each country and pooled SIRs were subsequently calculated for both any cancer and site-specific cancers of interest. Results A total of 5218, 2039, 270 and 526 patients were registered as ever TNFi-treated in ARTIS, DANBIO, ICEBIO and ROB-FIN, respectively, contributing a total of 44 041 patient years of follow-up across all 4 countries. For all cancers, the SIRs of TNFi-treated patients from ARTIS, DANBIO, ICEBIO and ROB-FIN were 0.94 (0.80 to 1.10), 0.99 (0.77 to 1.26), 1.71 (0.88 to 2.99) and 1.28 (0.82 to 1.90), respectively. The number of observed and expected cancers and the SIRs of any and selected site-specific cancers are listed in table 1. Conclusion Our results suggest that the overall cancer risk for TNFi-treated PsA patients is not increased compared to the general population. Further analysis of the risk of malignant lymphomas will inform on whether the increased risk we observed is attributed to the PsA disease or treatment with TNFi. Acknowledgement This study is funded by FOREUM and NordForsk. Disclosure of Interests Christine Ballegaard Speakers bureau: Janssen Pharmaceuticals., Karin Hellgren: None declared, Rene Cordtz: None declared, Benedicte Delcoigne: None declared, Bjorn Gudbjornsson: None declared, Thorvardur Jon Love Consultant for: Received reimbursment from Celgene for speaking about guidelines for the treatment of psoriatic arthritis, Kalle Aaltonen: None declared, Dan Nordstrom Grant/research support from: MSD, Pfizer, Consultant for: AbbVie, BMS, MSD, Novartis, Roche, Pfizer, UCB, Speakers bureau: Novartis, UCB, Sella Aarrestad Provan Consultant for: Novartis, Speakers bureau: Lilly, Johan Askling Grant/research support from: Karolinska Institutet (JA) has or has had research agreements with the following pharmaceutical companies, mainly in the context of the ATRIS national safety monitoring programme for rheumatology biologicals: Abbvie, BMS, MSD, Eli Lilly, Pfizer, Roche, Samsung Bioepis, and UCB., Consultant for: Karolinska Institutet has received remuneration for JA participating in ad boards arranged by Lilly, Novartis, and Pfizer., Kristian Zobbe: None declared, Lars Erik Kristensen Grant/research support from: UCB, Biogen, Janssen Pharmaceuticals, and Novartis, Consultant for: Consultant for AbbVie, Amgen, Biogen, BMS, Celgene, Eli Lilly, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB Pharma., Speakers bureau: Pfizer, AbbVie, Amgen, UCB, BMS, Biogen, MSD, Novartis, Eli Lilly and Company, and Janssen Pharmaceuticals, Lene Dreyer Consultant for: MSD, UCB and Janssen Pharmaceuticals, Speakers bureau: MSD, UCB and Janssen Pharmaceuticals, Speakers bureau: UCB, MSD, Eli Lilly and Janssen Pharmaceuticals.

Background: The optimal sequencing of biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in Rheumatoid Arthritis (RA) is unknown. Evidence regarding the effectiveness of a 2nd non-TNFi bDMARD, as well as of TNFi, in patients whose 1st bDMARD has been a non-TNFi is limited. Objectives: To characterize patients switching for medical reasons after failure of a non-TNFi used as 1st bDMARD, and to assess the effectiveness of rituximab (RTX), abatacept (ABA) or tocilizumab (TCZ) vs. a TNFi. Methods: Patients from 5 national registers (Sweden, Norway, Denmark, Iceland and Finland) with RA who started treatment with a non-TNFi as a 1st bDMARD after 2010 and switched to a 2nd bDMARD within 3 months after the discontinuation of the 1st (with the exception of RTX for which a 6-month window was used), were identified. Clinical effectiveness was assessed by DAS28 change at 6 months. Results: 611 patients were included in the analyses. 80% were female, the majority were positive for RF (76%) and anti-CCP (69%). The mean (±SD) age, DAS28 and HAQ at baseline was 58 (13), 4.5 (1.4) and 1.3 (0.7), respectively, while the median (IQR) disease duration was 5.0 (2.2-12.0) years. Baseline characteristics of patients and the clinical response for each switching strategy are shown in table 1. Moderate responses were observed for most switching strategies. 63% of patients were still on treatment with their 2nd bDMARD at 6 months after switch. Conclusion: The six-month drug retention for a 2nd bDMARD in patients with RA switching due to failure of a non-TNFi bDMARD as 1st ever bDMARD was lower than two thirds (63%). More detailed analyses are exploring potential subgroups of patients for whom specific switching strategies are more effective. Acknowledgement: The study was partly funded by a study grant from NordForsk and Foreum. Disclosure of Interests: Katerina Chatzidionysiou: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen, Pfizer, Consultant for: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck, Samsung Bioepis, Thomas Frisell: None declared, Daniela Di Giuseppe: None declared, Karin Hellgren: None declared, Bente Glintborg Grant/research support from: Biogen, Pfizer, AbbVie, Dan Nordstrom Grant/research support from: MSD, Pfizer, Consultant for: AbbVie, BMS, MSD, Novartis, Roche, Pfizer, UCB, Speakers bureau: Novartis, UCB, Kalle Aaltonen: None declared, Nina Trokovic: None declared, Eirik kristianslund: None declared, Tore K. Kvien Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB., Consultant for: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Oktal, Orion Pharma, Pfizer, Roche, Sandoz, Sanofi, Mylan and UCB, Speakers bureau: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Oktal, Orion Pharma, Pfizer, Roche, Sandoz, Sanofi and UCB, Sella Aarrestad Provan Consultant for: Novartis, Speakers bureau: Lilly, Bjorn Gudbjornsson: None declared, Gerdur Grondal : None declared, Lene Dreyer Consultant for: MSD, UCB and Janssen Pharmaceuticals, Speakers bureau: MSD, UCB and Janssen Pharmaceuticals, Speakers bureau: UCB, MSD, Eli Lilly and Janssen Pharmaceuticals., Lars Erik Kristensen Grant/research support from: UCB, Biogen, Janssen Pharmaceuticals, and Novartis, Consultant for: Consultant for AbbVie, Amgen, Biogen, BMS, Celgene, Eli Lilly, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB Pharma., Speakers bureau: Pfizer, AbbVie, Amgen, UCB, BMS, Biogen, MSD, Novartis, Eli Lilly and Company, and Janssen Pharmaceuticals, Tanja Schjodt Jorgensen Consultant for: Abbvie, Roche, Novartis, UCB, Biogen, Eli Lilly., Speakers bureau: Abbvie, Roche, Novartis, UCB, Biogen, Eli Lilly., Lennart T.H. Jacobsson Consultant for: LJ has received lecture and consulting fees from Pfizer, Abbvie, Novartis, Eli-Lily and Janssen, Johan Askling Grant/research support from: Karolinska Institutet (JA) has or has had research agreements with the following pharmaceutical companies, mainly in the context of the ATRIS national safety monitoring programme for rheumatology biologicals: Abbvie, BMS, MSD, Eli Lilly, Pfizer, Roche, Samsung Bioepis, and UCB., Consultant for: Karolinska Institutet has received remuneration for JA participating in ad boards arranged by Lilly, Novartis, and Pfizer.

Background The first infliximab biosimilar (CT-P13) was introduced in Europe in 2014, followed by a rapid, but differential, uptake across the Nordic countries [1]. Pre and post-marketing randomized controlled trials have shown similar efficacy and safety of originator infliximab (INF) versus CT-P13, but a number of observational studies have indicated potential differences in long-term treatment retention. However, no large observational study has hitherto directly compared the treatment retention of INF with CT-P13 in bio-naive patients with spondyloarthritis (SpA) starting infliximab during the same calendar-time period. Objectives To compare one- and two-year treatment retention of INF versus CT-P13 in SpA, when used as a first line biologic, and to explore baseline characteristics in the two cohorts. Methods Observational cohort study. Bio-naive patients with ankylosing spondylitis (AS), non-radiographic axial SpA (nrax-SpA) or undifferentiated SpA (uSpA), starting INF or CT-P13 as their first ever TNFi during the time-period Jan 2014 through Jun 2017 were identified in biological registers in the five Nordic countries. SpA comorbidities were identified through linkage to national registers. Treatment retention of INF versus CT-P13 was assessed through survival probability curves and one- and two-year retention rates. Results In total 1319 bio-naive patients with SpA started infliximab during the time-period, 24% started INF and 76% CT-P13. Baseline characteristics of patients in the two treatment groups were comparable (Table 1). The survival probability curves were identical for INF compared to CT-P13 (Figure 1), and the proportion of patients remaining on treatment after one and two years were similar: one year INF 62% (95%CI 57-68%), CT-P13 63% (95%CI 60-66%); two years: INF 44% (95%CI: 38-50%) and CT-P13 46% (95%CI: 42-51%). Further confounder-adjusted analyses, are planned and will be presented at the conference. Conclusion We found remarkably similar treatment retentions for the infliximab originator and biosimilar when used as the first line biologic in 1319 patients with SpA. The baseline characteristics of the patients starting the originator and the biosimilar suggest that the cohorts are comparable, and the results thus supports the equivalence of the treatments. Reference [1] Glintborg, et al. Biological treatment in ankylosing spondylitis in the Nordic countries during 2010-2016: a collaboration between five biological registries. Scand J Rheumatol. 2018;47:465-74. Acknowledgement This study received funding from NordForsk and from FOREUM. Disclosure of Interests Ulf Lindstrom: None declared, Bente Glintborg Grant/research support from: Biogen, Pfizer, AbbVie, Daniela Di Giuseppe: None declared, Johan Askling Grant/research support from: Karolinska Institutet (JA) has or has had research agreements with the following pharmaceutical companies, mainly in the context of the ATRIS national safety monitoring programme for rheumatology biologicals: Abbvie, BMS, MSD, Eli Lilly, Pfizer, Roche, Samsung Bioepis, and UCB., Consultant for: Karolinska Institutet has received remuneration for JA participating in ad boards arranged by Lilly, Novartis, and Pfizer., Dan Nordstrom Grant/research support from: MSD, Pfizer, Consultant for: AbbVie, BMS, MSD, Novartis, Roche, Pfizer, UCB, Speakers bureau: Novartis, UCB, Sella Aarrestad Provan Consultant for: Novartis, Speakers bureau: Lilly, Bjorn Gudbjornsson: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen, Pfizer, Consultant for: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck, Samsung Bioepis, Kalle Aaltonen: None declared, Niels Steen Krogh: None declared, Arni Jon Geirsson: None declared, Lennart T.H. Jacobsson Consultant for: LJ has received lecture and consulting fees from Pfizer, Abbvie, Novartis, Eli-Lily and Janssen

Background The marketing approval of the etanercept biosimilar SB4 was based on phase III studies on patients with rheumatoid arthritis, but extended to all etanercept indications. Currently, no randomized controlled trials have compared etanercept originator (ETN) with SB4 in patients with spondyloarthritis (SpA). However, the uptake of etanercept biosimilars in the treatment of SpA has been exponential in the Nordic countries, with marked differences across the countries [1]. Objectives To compare the one-year treatment retention in bio-naive patients with SpA treated with ETN versus SB4. Furthermore, to explore baseline characteristics in the two patient groups. Methods Observational cohort study. Patients with SpA (ankylosing spondylitis (AS), non-radiographic axial SpA (nrax-SpA) or uSpA)), starting etanercept as their first ever TNFi Jan 2014 through Jun 2017 were identified in biologics registers in the five Nordic countries. Baseline characteristics were retrieved from each biological register and comorbidity data through linkage to national registers. The country-specific data were then pooled for further analysis. Comparisons of treatment retention between ETN and SB4 were assessed through survival probability curves and one-year retention rates. Results In total, 1015 patients were included, whereof 49% started ETN and 51% SB4. Baseline characteristics were similar in the two patient groups (Table?1). One-year survival probability curves were similar for ETN compared to SB4 (Figure 1), and the proportions of patients remaining on drug after one year were comparable: ETN 66% (95%CI: 61-70%) and SB4 73% (95%CI: 68-78%). Further confounder-adjusted analyses are planned and will be presented at the conference. Conclusion In this observational study of 1015 patients with SpA from five Nordic countries, biologics-naive patients starting treatment with originator versus biosimilar etanercept had similar baseline characteristics and similar one-year treatment retention rates, suggesting similar effectiveness and tolerability of the two drugs. Reference [1] Glintborg, et al. Biological treatment in ankylosing spondylitis in the Nordic countries during 2010-2016: a collaboration between five biological registries. Scand J Rheumatol. 2018;47:465-74. Acknowledgement This study received funding from NordForsk and from FOREUM. Disclosure of Interests Bente Glintborg Grant/research support from: Biogen, Pfizer, AbbVie, Ulf Lindstrom: None declared, Daniela Di Giuseppe: None declared, Johan Askling Grant/research support from: Karolinska Institutet (JA) has or has had research agreements with the following pharmaceutical companies, mainly in the context of the ATRIS national safety monitoring programme for rheumatology biologicals: Abbvie, BMS, MSD, Eli Lilly, Pfizer, Roche, Samsung Bioepis, and UCB., Consultant for: Karolinska Institutet has received remuneration for JA participating in ad boards arranged by Lilly, Novartis, and Pfizer., Dan Nordstrom Grant/research support from: MSD, Pfizer, Consultant for: AbbVie, BMS, MSD, Novartis, Roche, Pfizer, UCB, Speakers bureau: Novartis, UCB, Sella Aarrestad Provan Consultant for: Novartis, Speakers bureau: Lilly, Bjorn Gudbjornsson: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen, Pfizer, Consultant for: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck, Samsung Bioepis, Kalle Aaltonen: None declared, Arni Jon Geirsson: None declared, Niels Steen Krogh: None declared, Lennart T.H. Jacobsson Consultant for: LJ has received lecture and consulting fees from Pfizer, Abbvie, Novartis, Eli-Lily and Janssen

Background A research network collaboration of 15 European registries sharing data on patients with spondyloarthitis (SpA), “EuroSpA”, has recently been created to strengthen research capabilities in the real world setting1. Here we present the first results from the collaboration. Objectives To investigate the feasibility of creating a common database for axial SpA (axSpA), including non-radiographic SpA and ankylosing spondylitis, within the EuroSpA collaboration and to conduct proof-of-concept analyses by investigation of baseline characteristics, disease activity at baseline and after 6 months, and crude 12 months’ Tumour Necrosis Factor inhibitor (TNFi) retention rate in patients with axSpA initiating TNFi. Methods A common data model was agreed upon by the EuroSpA Scientific Committee. Virtual meetings between the EuroSpA and registry data managers clarified data availability and structure. This was followed by upload of anonymized data through the secure Virtual Private Network pipelines to the EuroSpA server. Baseline characteristics and disease activity at baseline and after 6 months were investigated with non-parametric descriptive statistics. Kaplan-Meier estimation was used to investigate TNFi retention rates. Results By January 8th 2018, four of the 15 registries participating in EuroSpA had completed data upload to the EuroSpA database resulting in 6756 patients with AxSpA in a pooled dataset. Baseline characteristics of the participating registry populations at initiation of first TNFi are shown in Table I. Crude 12 months’ TNFi retention rate varied from 66%–85% for 1 st TNFi and 61%–78% for 2nd TNFi (see figure 1). For the pooled dataset crude 12 months’ TNFi retention rates were 73% and 66% for the 1 st and 2nd TNFi, respectively. Conclusions Preliminary analyses showed differences across European registries regarding baseline characteristics and crude retention rates in axSpA patients initiating TNFi. These initial, preliminary analyses demonstrate that the creation of a large European database of axSpA patients treated in routine care based on a common data model is feasible, offering important opportunities for future research. Reference [1] Ann Rheum Dis2017;(suppl. 2):65. Acknowledgements The authors acknowledge Novartis Pharmaceuticals AG for financial support and Natasha Pillai and Carol Lines from QuintilesIMS and Craig Richardson from Novartis Pharmaceuticals AG for their assistance in setting up the EuroSpA collaboration. Disclosure of Interest L. Ornbjerg: None declared, M. Ostergaard: None declared, F. Onen: None declared, G. Can: None declared, Z. Rotar: None declared, M. Tomsic Consultant for: AbbVie, Eli Lilly, Johnson and Johnson, Medis, MSD, Novartis, Pfizer and Roche, B. Gudbjornsson: None declared, A. Geirsson: None declared, M. Santos: None declared, A. Barcelos: None declared, D. Nordstrom Consultant for: AbbVie, Celgene, BMS, Lilly, MSD, Novartis, Pfizer, UCB, K. Aaltonen: None declared, M. J. Nissen: None declared, A. Ciurea: None declared, E. Kristianslund: None declared, T. Kvien Grant/research support from: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Epirus, Hospira, Merck-Serono, MSD, Mundipharma, Novartis, Orion Pharma, Hospira/Pfizer, Sandoz, UCB, C. Codreanu: None declared, E.-M. Hauge: None declared, L. Jacobsson: None declared, H. Mann: None declared, G. Jones: None declared, F. Iannone: None declared, M. V. Hernandez: None declared, I. van der Horst-Bruinsma: None declared, L. H. Hyldstrup: None declared, N. S. Krogh: None declared, M. Hetland Grant/research support from: AbbVie, Biogen, BMS, CellTrion, MSD, Orion, Pfizer, Samsung, UCB

There are increasing needs for detailed real-world data on rheumatic diseases and their treatments. Clinical register data are essential sources of information that can be enriched through linkage to additional data sources such as national health data registers. Detailed analyses call for international collaborative observational research to increase the number of patients and the statistical power. Such linkages and collaborations come with legal, logistic and methodological challenges. In collaboration between registers of inflammatory arthritides in Sweden, Denmark, Norway, Finland and Iceland, we plan to enrich, harmonise and standardise individual data repositories to investigate analytical approaches to multisource data, to assess the viability of different logistical approaches to data protection and sharing and to perform collaborative studies on treatment effectiveness, safety and health-economic outcomes. This narrative review summarises the needs and potentials and the challenges that remain to be overcome in order to enable large-scale international collaborative research based on clinical and other types of data.

Objective.Because of the role of tumor necrosis factor (TNF) in host defense, it was hypothesized that its inhibition might lead to an increased risk of malignancies and infections. The objective of our study was to assess the incidence of serious infections leading to hospitalization and malignancies among patients with rheumatoid arthritis (RA) receiving either TNF inhibitor or rituximab (RTX) therapy.Methods.The study population was identified from the National Register for Biologic Treatment in Finland and the hospital records of Central Finland Central Hospital for conventional disease-modifying antirheumatic drug (cDMARD) users. Data on infections and malignancies were acquired from national healthcare registers. A Poisson model was used to calculate the adjusted incidence rate ratios (aIRR) and was composed of age, sex, time from diagnosis, year of the beginning of the followup, rheumatoid factor status, Disease Activity Score at 28 joints, Health Assessment Questionnaire, prior malignancy, prior serious infection, prior biologic use, and time-updated use of methotrexate, sulfasalazine, hydroxychloroquine, and oral corticosteroids as confounders.Results.In total, during the followup of 10,994 patient-years, 92 malignancies and 341 serious infections were included in the analyses. The aIRR of infections compared to cDMARD users were 1.2 (95% CI 0.63–2.3), 0.84 (95% CI 0.53–1.3), 0.98 (95% CI 0.60–1.6), and 1.1 (95% CI 0.59–1.9) for the patients treated with infliximab (IFX), etanercept, adalimumab, and RTX, respectively. The crude rates of malignancies were highest among the users of cDMARD and RTX, and lowest among patients treated with IFX with no differences in aIRR.Conclusion.Our results provide some reassurance of the safety of biologic treatments in the treatment of RA.

Background Psoriatic arthritis (PsA) is a chronic inflammatory disorder associated with skin and joint manifestations, several extra-articular symptoms, various comorbidities, and disability. The emergence of tumour necrosis factor inhibitor (TNFi) therapy has dramatically changed the course of disease. Over the past decade new TNFi therapies have emerged (certolizumab pegol and golimumab), and recently ustekinumab and secukinumab have also become available for PsA. Objectives The objective of this study was to assess the relative use of biological agents (bDMARDs) in PsA from 2006 through 2014, using data from the Nordic Rheumatology registers. Methods Based on data from the observational registers DANBIO, ICEBIO, NOR-DMARD, ROB-FIN, and SRQ registers, PsA patients initiating treatment with bDMARDs as a first or subsequent biological therapy were identified. Adalimumab, etanercept and infliximab were grouped as “first generation TNFi therapies”; certolizumab pegol and golimumab were grouped as “second generation TNFi”. Treatments with ustekinumab during the study period were also identified. Descriptive statistics for prescription patterns of bDMARD therapy were calculated. Results A total of 11,458 treatment initiations were identified (DANBIO 3,068, ICEBIO 357, NOR-DMARD 1,113, ROB-FIN 708, SRQ 6,212). 54% of the patients were female. Overall, 5,695 patients initiated a first generation TNFi, 912 a second generation TNFi, and 16 ustekinumab, as their first course of biological treatment. The corresponding numbers for those initiating a second (or more) biological treatment were 3,606, 1,090 and 139 patients, respectively. The figure displays the annual number of treatment initiations stratified by treatment type. The total yearly number of first course biological treatment increased significantly throughout the period (p Conclusions Across the Nordic countries the prescription pattern for biological therapies for PsA has changed significantly over time. After 2012 initiation of the first generation TNFi is decreasing both as first and second course therapy, whereas second generation TNFi are increasing both as first and second course of biologic intervention. Collaboration across registers will allow for robust assessment of the uptake of newer biological therapies. Acknowledgements This study was partly funded by a grant from NordForsk and Janssen Pharmaceuticals. Disclosure of Interest T. S. Jorgensen Speakers bureau: Abbvie, Roche, Novartis, UCB, Biogen, L. Dreyer Speakers bureau: MSD, UCB and Janssen Pharmaceuticals, B. Guðbjornsson Speakers bureau: Actavis, Celgene, MSD, Pfizer, M. Hetland Speakers bureau: BMS, MSD, AbbVie, Roche, Eli Lilly, Pfizer, Orion, Novartis, B. Glintborg Speakers bureau: Abbvie, J. Askling Grant/research support from: AstraZeneca, UCB, Lilly, Pfizer, Roche, Merck,Samsung, Janssen, K. Chatzidionysiou Speakers bureau: AbbVie, Pfizer, Eli Lilly, UCB, Roche., D. Di Giuseppe: None declared, L. Jacobsson Consultant for: Abbvie, Celegen, MSD, Novartis and UCB, J. Wallman Consultant for: Novartis, Celgene, UCB, E. Kristianslund: None declared, I. Olsen: None declared, K. Fagerli: None declared, E. Lie Speakers bureau: AbbVie, Celgene, Hospira and Pfizer., D. Nordstrom Speakers bureau: AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, UCB., K. Aaltonen: None declared, J. Joensuu Speakers bureau: Pfizer., T. J. Love: None declared, A. J. Geirsson: None declared, L. E. Kristensen Speakers bureau: Pfizer, AbbVie, Amgen, UCB, Celgene, BMS, MSD

Background and objectives: Tumor necrosis factor (TNF)-inhibitors are used to treat psoriatic arthritis (PsA), but only a limited number of observational studies on this subject have been published thus far. The aim of this research was to analyze the effectiveness and drug survival of TNF-inhibitors in the treatment of PsA. Methods: PsA patients identified from the National Register for Biologic Treatment in Finland (ROB-FIN) starting their first, second, or third TNF-inhibitor treatment between 2004 and 2014 were included. Effectiveness was measured using ACR and EULAR response criteria and modeled using ordinal logistic regression. Treatment persistence was analyzed using Kaplan-Meier survival analysis and Cox proportional hazards model. Results: The study comprised 765 patients and 990 TNF-inhibitor treatment courses. EULAR moderate treatment responses at 6 months were achieved by 68% and 37% of the users of the first and the second or the third biologic, respectively. The probabilities of discontinuing the treatment within 12 and 24 months were 20% and 28%, respectively. Adjusted treatment responses to all TNF-inhibitors were similar; however, co-therapy with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) was not associated with better effectiveness. Adalimumab [hazard ratio (HR) = 0.62; 95% confidence interval (CD: 0.44-0.88] was superior to infliximab in drug survival while etanercept (HR = 0.77, 95% CI: 0.55-1.1) and golimumab (HR = 0.75, 95% CI: 0.46-1.2) did not differ from it. Co-medication with csDMARDs did not statistically improve drug survival. Conclusion: All available TNF-inhibitors showed similar treatment responses with or without csDMARDs. Adalimumab was associated with better drug survival when compared to infliximab. (C) 2017 Elsevier Inc. All rights reserved.

Background Large-scale real life observational cohorts are needed to study effectiveness and early signals of rare safety issues of new biological disease modifying drugs (bDMARDs) and biosimilars (bsDMARDs) in ankylosing spondylitis (AS). Combining data from biological registries would facilitate this. The Nordic countries have several similarities that would justify such aggregated analyses including similar health care systems with universal access to population based health care, availability of b/bsDMARDs through a tax-paid system and the registration of use and effectiveness of bDMARDs in inflammatory diseases in a prospective manner in drug registries. Objectives To explore the prescription patterns of old (TNF-inhibitors) and newer bDMARDs (secukinumab, ustekinumab) including bsDMARDs (SB4, CT-P13) over time in AS in the Nordic countries in order to illustrate the potential of a common Nordic collaboration. Methods Data regarding the numbers of AS patients (pts) (ICD10 code M45) who initiated bDMARD treatment (irrespective of treatment course number) during the period 2011–2016 were collected from the Nordic rheumatologic biological registries SRQ (Sweden), NOR-DMARD (6 Norwegian treatment centres), DANBIO (Denmark), ROB-FIN (Finland, 2011–2015) and ICEBIO (Iceland). Results In total, 6,610 bDMARD treatment initiations were identified (Sweden 3654, Norway 1078, Denmark 782, Finland 789, Iceland 307). The prescription patterns of bDMARDs changed substantially over time. In 2016, the number of pts initiating a bsDMARDs exceeded those starting an originator bDMARD (figure). Few patients were treated with ustekinumab (Denmark Conclusions The use of bsDMARDs in AS is rapidly increasing. The use of drugs with new modes of action is still low, which illustrates the need for collaboration across countries to provide real life data with sufficient power for new innovative therapies in the future. The Nordic rheumatologic registries represent a unique opportunity to study effectiveness and safety of bDMARDs, including bsDMARDs in AS. Acknowledgements Partly funded by a grant from NordForsk Disclosure of Interest B. Glintborg Grant/research support from: abbvie, K. Chatzidionysiou: None declared, J. Askling Grant/research support from: AbbVie, Eli Lilly, Janssen, Merck, Pfizer, Roche, UCB, Samsung, K. Aaltonen Speakers bureau: AbbVie, BMS, Janssen, MSD, Pfizer, Roche, UCB, E. Kristianslund: None declared, B. Gudbjornsson Grant/research support from: Actavis, Celgene, MSD, Pfizer, D. Nordstrom Speakers bureau: AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, UCB, M. Hetland Grant/research support from: Orion, BMS, AbbVie, Biogen, Pfizer, MSD, L. Dreyer Speakers bureau: MSD, UCB, Janssen Pharmaceuticals, L. E. Kristensen Speakers bureau: Pfizer, AbbVie, Biogen, Amgen, UCB, Celegene, BMS, MSD, Novartis, Eli Lilly, Janssen pharmaceuticals, T. Jorgensen Speakers bureau: AbbVie, Roche, Novartis, UCB, Biogen, K. Eklund: None declared, G. Grondal: None declared, S. Ernestam: None declared, J. Joensuu Grant/research support from: Pfizer, T. Kvien Speakers bureau: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz, UCB, E. Lie Speakers bureau: AbbVie, Celgene, Hospira, Pfizer, K. Fagerli: None declared, A. J. Geirsson: None declared, H. Jonsson: None declared, L. Jacobsson Consultant for: Abbvie, Celegen, MSD, Novartis, UCB

Objective: A systematic review found that an average of 27% of rheumatoid arthritis (RA) patients using tumour necrosis factor (TNF) inhibitors discontinue their treatment within 1year. The aim of this study was to assess drug survival on TNF inhibitors among patients with RA.Methods: Patients were identified from the National Register for Biologic Treatment in Finland (ROB-FIN), which is a longitudinal cohort study established to monitor the effectiveness and safety of biologic drugs in rheumatic diseases. Inclusion was limited to TNF-inhibitor treatments started as the patient's first, second, or third biologic treatment between 2004 and 2014. Follow-up was truncated at 36months. The results of a time-dependent Cox proportional hazards model were reported as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs).Results: Of the 4200 TNF-inhibitor treatment periods identified from ROB-FIN, 3443 periods from 2687 patients met the inclusion criteria. Twenty-seven per cent of the patients discontinued their treatment within 12months. Infliximab (HR 1.8, 95% CI 1.3-2.5) and certolizumab pegol (HR 1.7, 95% CI 1.2-2.3) had lower drug survival compared to golimumab. A similar trend was seen with adalimumab (HR 1.2, 95% CI 0.90-1.7) and etanercept (HR 1.2, 95% CI 0.87-1.6). Concomitant use of methotrexate (MTX) was associated with improved drug survival (HR 0.76, 95% CI 0.64-0.90) in comparison with TNF-inhibitor monotherapy.Conclusions: Golimumab was better in terms of drug survival than infliximab or certolizumab pegol and at least as good as adalimumab and etanercept. Concomitant use of MTX improved drug survival on TNF inhibitors.

The aim was to study the incidence of joint replacements among biologic drug and disease-modifying anti-rheumatic drug (DMARD) users as well as to investigate the plausible effect of biologic treatment on survival of prostheses in patients with Rheumatoid arthritis (RA).The study population comprised 2 cohorts of patients [Register of biologic treatment in Finland (ROB-FIN) and the Central Finland RA database] from 1999 to 2010. Records of joint replacements performed in the study population between 1980 and 2010 were retrieved from the Finnish Arthroplasty Register. Propensity score matching was used to equalize patient characteristics between biologics and DMARD users. The incidence rates of primary and revision operations were compared between the 2 treatment groups. Kaplan-Meier survival analysis was used to analyze prosthesis survival.Of the 2102 biologics and 2710 DMARD users identified from the registries, 1587 were included in both groups after the matching. Median follow-up times were 3.1 and 8.0 years, respectively. There were more primary operations per 100 patient years in the biologics (3.89, CI 95% 3.41-4.41) vs. DMARD (2.63, 2.35-2.94) group but slightly fewer revisions (0.65, 0.46-0.88 vs. 0.83, 0.68-1.01). Biologics users were more likely to receive a joint replacement to small joints (p0.001). The survival of the prostheses installed during or prior to follow-up was similar in both treatment groups.The use of biologic drugs did not reduce the need for joint replacement surgery in patients with a similar on-medication disease activity. Despite possibly lower rate of revisions among biologic users, the durability of prostheses was not improved.

Objective Efficacy of TNF inhibitors in the treatment of RA assessed in randomized controlled trials (RCTs) may not be fully comparable to routine care owing to the stringent inclusion criteria. The objective of this study was to observe the effectiveness of TNF inhibitors in real-world patients and assess the patients' potential eligibility for the RCTs. Methods RA patients starting a TNF-inhibitor treatment between 2004 and 2014 were identified from the National Register for Biologic Treatment in Finland, which is a longitudinal observational cohort study. Effectiveness was measured using the ACR and EULAR response criteria and by studying the proportion of patients reaching DAS28 remission. The patients' baseline characteristics were compared against the inclusion criteria of 27 RCTs. Results EULAR moderate and good treatment responses at 6 months were achieved by 69 and 40% of the users of the first TNF inhibitor, respectively. ACR20, ACR50 and ACR70 responses were reached by 48, 27 and 13%, respectively. DAS28 remission was reached by 47%. Only 7.6-44% of the patients would have been potentially eligible for the RCTs. The eligible patients had better treatment responses compared with the non-eligible patients. Different TNF inhibitors were mostly equipotent, but the usage of MTX co-therapy had a major influence on treatment response. Conclusion Only a small proportion of patients would have been eligible for RCTs, and the efficacy of TNF inhibitors assessed in them cannot be generalized directly into Finnish routine health care.

Objective The aim of this study was to explore the cost-effectiveness of biological DMARDs (bDMARDs) compared with conventional synthetic DMARDs (csDMARDs) for RA using real-world data from Finnish registers. Methods RA patients starting their first bDMARD and comparator patients using csDMARDs during 2007-11 were obtained from the National register of biologic treatments in Finland and the Jyvaskyla Central Hospital patient records. Propensity score matching was applied to adjust for differences between bDMARD and csDMARD users. Effectiveness was measured in quality-adjusted life years (QALY) and based on the register of biologic treatments in Finland and Jyvaskyla Central Hospital patient records, whereas the direct costs were obtained from relevant Finnish national registers. Patients were followed up for 2 years, and both costs and effectiveness for the second year were discounted at 3%. The incremental cost-effectiveness ratio (ICER) with 95% CI was calculated based on bootstrapped mean costs and effectiveness. Results Of 1581 RA patients meeting study inclusion criteria, 552 bDMARD and 220 csDMARD users were included in analyses after matching. Mean costs for bDMARDs and csDMARDs were €55 371 and €24 879, while mean effectiveness was 1.23 and 1.20 QALYs, respectively. Consequent ICER was €902 210/QALY. Results were confirmed in sensitivity analyses. Conclusion The high incremental cost and the small, non-significant difference in effectiveness resulted in high ICER, suggesting that bDMARDs are not cost-effective. Regardless of matching, latent confounders may introduce bias to the results.

Objective.The aim of this research was to describe the effectiveness and drug survival of tumor necrosis factor (TNF) inhibitors in the treatment of ankylosing spondylitis (AS) and to analyze the effect of concomitant treatment with conventional disease-modifying antirheumatic drugs.Methods.Patients with AS identified from the National Register for Biologic Treatment in Finland starting their first TNF inhibitor treatment between July 2004 and December 2011 were included. Treatment response was measured as an improvement of 50% (or 20 mm) after 6 months of treatment onset compared to the baseline Bath AS Disease Activity Index (BASDAI) score. Treatment response and 2-year drug survival were modeled with logistic regression and time-dependent Cox proportional hazard models, respectively.Results.The study comprised 543 patients, of whom 123 also commenced a second TNF inhibitor during the followup. Treatment was discontinued within 24 months by 25% and 28% of the users of the first and the second TNF inhibitors, respectively. BASDAI response at 6 months was achieved by 52% and 25% of the users of the first and the second TNF inhibitors, respectively. Etanercept (ETN; HR 0.42, 95% CI 0.29–0.62) and adalimumab (ADA; HR 0.48, 95% CI 0.30–0.77) were associated with better drug survival in comparison to infliximab (IFX). Also, concurrent use of sulfasalazine (SSZ; HR 0.70, 95% CI 0.49–0.99) decreased the hazard for treatment discontinuation.Conclusion.TNF inhibitors are equipotent in the treatment of AS; however, ETN and ADA were found superior to IFX in drug survival. The use of SSZ improves treatment continuation.

Item does not contain fulltext OBJECTIVE: Under the auspices of the European League Against Rheumatism (EULAR), a study group of investigators representing European biologic DMARD (bDMARD) registers was convened. The purpose of this initial assessment was to collect and compare a cross section of patient characteristics and collate information on the availability of potential confounders within these registers. METHODS: Baseline characteristics of patients starting their first bDMARD in an arbitrary year (2008) for the treatment of RA, including demographic and disease characteristics, bDMARD drug details and co-morbidities, were collected and compared across 14 European bDMARD registers. RESULTS: A total of 5320 patients were included. Half the registers had restricted recruitment to certain bDMARDs during the study year. All registers` collected data on age, gender, disease duration, seropositivity for IgM-RF and 28-joint DAS (DAS28). The mean DAS28 ranged from 4.2 to 6.6 and the mean HAQ from 0.8 to 1.9. Current smoking ranged from 9% to 34%. Nine registers reported co-morbidities with varying prevalence. CONCLUSION: In addition to demonstrating European-wide collaboration across rheumatology bDMARD registers, this assessment identified differences in prescribing patterns, recruitment strategies and data items collected. These differences need to be considered when applying strategies for combined analysis. The lack of a common data model across Europe calls for further work to harmonize data collection across registers.

Background Previous studies have found that 26 to 34% of Rheumatoid Arthritis (RA) patients using Tumor Necrosis Factor (TNF)-inhibitors discontinue their treatment within one year [1,2]. Infliximab has been associated with poorer drug survival as compared to adalimumab and etanercept. Objectives The aim of this study was to assess the drug survival on TNF-inhibitors including golimumab and certolizumab pegol among patients with RA and the effect of co-medication on drug survival. Methods Patients were identified from the National Register for Biologic Treatment in Finland (ROB-FIN), which is a longitudinal cohort study established in 1999 to monitor the effectiveness and safety of Biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in rheumatic diseases. Inclusion was limited to TNF-inhibitor treatments started as the patients9 first, second or third biologic treatment between 2004 and 2014. Missing baseline data was imputed by multiple imputation. Follow-up data was available until the end of 2015; however follow-up of individual treatment periods was truncated at 36 months. A Cox proportional hazards model with age as well as conventional synthetic DMARD (csDMARD) and glucocorticoid use as time-dependent confounders was carried out to compare the survival of individual TNF-inhibitors and to study the effect of co-medication. The results were reported as adjusted Hazard Ratios (HRs) with 95% Confidence Intervals (CI). Results Of the 4,067 TNF-inhibitor treatment periods identified from ROB-FIN, 3,345 periods from 2,641 patients met the inclusion criteria, accumulating a total of 5,620 patient years. Median baseline age and DAS28 score were 55 and 3.8, respectively while 74% of the included patients were women. Etanercept, adalimumab, infliximab, golimumab and certolizumab Pegol were used by 1320 (39%), 1306 (39%), 333 (10%), 195 (5.8%) and 191 (5.7%) patients, respectively. Infliximab (34%) and golimumab (20%) were associated with the highest and the lowest percentages of patients discontinuing their treatment within one year, respectively while the overall percentage was 23%. Infliximab (HR 2.2, 95% CI 1.6–3.1) and certolizumab pegol (HR 1.8, 95% CI 1.3–2.6) had lower drug survival when compared to golimumab. Similar although statistically non-significant trend was seen with adalimumab (HR 1.3, 95% CI 0.99–1.8) and etanercept (HR 1.4, 95% CI 0.99–1.8) as well. Concomitant use of methotrexate (MTX) with or without any additional csDMARDs was associated with improved drug survival (HR 0.78, 95% CI 0.66–0.92) in comparison with TNF-inhibitor monotherapy. Conclusions We found that golimumab was better in terms of drug survival than infliximab or certolizumab pegol and at least as good adalimumab and etanercept. Concomitant use of MTX improves drug survival on TNF-inhibitors. References Neovius M et al. Ann Rheum Dis 2015;74:354–60. Flouri I et al. Semin Arthritis Rheum 2014;43:447–57. Acknowledgement This study was sponsored by MSD. In addition, ROB-FIN has received financial support from the following pharmaceutical companies: Abbvie, Pfizer and Roche. Disclosure of Interest None declared

Background Previous studies have reported medication adherence ranging from 49.5% to 98.5% in patients with rheumatoid arthritis (RA) 1. Adherence to TNFi has been estimated to be 59%2. Non-adherence has been associated with poorer health outcomes, such as physical disability and increased need for health services. Objectives The aim of the study was to analyse adherence to self-injectable biologic disease-modifying antirheumatic drugs (bDMARDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids in Finnish RA patients using their first bDMARDs. Methods RA patients starting their first bDMARD in 2007–2011 were identified from the National Register for Biologic Treatment in Finland (ROB-FIN). Restriction to the patients with available baseline data and at least 360 days follow-up with their first bDMARD was made. Data on prescribed medication was recorded in ROB-FIN while medication claims were retrieved from the register of the Social Insurance Institution of Finland. The proportion of days covered (PDC) during a 360-day period was calculated to define adherence. Patient was considered adherent if PDC was ≥80%. Results Fifty-two percent (n=424) of the 823 patients remained on the first bDMARD and were followed for at least 360 days. Forty-three percent of them (205) were adherent to all prescribed anti-rheumatic medication. CsDMARDs were prescribed to 372 patients of which 53% (196) were adherent while 5% (20) claimed no cdDMARD at all. Methotrexate was the most common csDMARD and was prescribed to 281 patients. The proportions of patients adherent to methotrexate and patients who claimed no methotrexate at all were 60% (170) and 9% (26), respectively. Self-injectable bDMARDs were prescribed to 319 of which 59% (187) were adherent and 8% (25) did not claim any of the prescribed bDMARD. Mean PDC for csDMARDs, methotrexate and self-injectable bDMARDs were 73%, 74% and 74%, respectively. Conclusions Less than half of the RA patients using bDMARDs were adherent to their antirheumatic medication. However, the current data measures only the medication claims instead of actual use. Moreover, the high proportion of patients lost to follow-up may cause bias to the results. References Pasma A, van9t Spijker A, Hazes JMW, et al. Factors associated with adherence to pharmaceutical treatment for rheumatoid arthritis patients: a systematic review. Semin Arthritis Rheum. United States; 2013 Aug;43(1):18–28. Fidder HH, Singendonk MMJ, van der Have M, et al. Low rates of adherence for tumor necrosis factor-alpha inhibitors in Crohn9s disease and rheumatoid arthritis: results of a systematic review. World J Gastroenterol. China; 2013 Jul;19(27):4344–50. Acknowledgement ROB-FIN has received restricted financial support from Abbvie, Roche, MSD and Pfizer. Disclosure of Interest None declared

Background Finnish national combination treatment trials [1,2] have demonstrated excellent outcomes in patients with early rheumatoid arthritis (RA) including 90% of patients reaching 28-joint Disease Activity Score (DAS28) remission. Whether similar results are reached in clinical praxis is not known. Objectives To assess what proportion of patients with dmard-naive early rheumatoid artritis (RA) reach DAS28 remission over one year and remission variability across clinics in Finland Methods Patients with dmard-naive inflammatory arthritis diagnosed as new early RA were recruited. Comparison among sites were made in proportion of patients in 28-joint Disease Activity Score with 3 variables (DAS28–3) remission. Repeated measures were analyzed using mixed models approach with appropriate distribution and link function. Results 611 patients were recruited at 5 sites: 67% female; the mean age (SD) at diagnosis was 57 (16) years; respective 71% and 68% were RF and AntiCCP positive; 23% had radiographic erosions. A total of 506 (83%) fulfilled the ACR/EULAR 2010 classification criteria for RA for further analyses. DAS28–3 remission was met by 68% and 75% at 3 and 12 mo, respectively. Clinic had no effect in remission when adjusted for confounders (Figure 1). At baseline, a total of 68% used MTX based combination therapy, and 31% used triple therapy with methotrexate, hydroxychloroquine and sulphasalazine. In multivariate analysis, the only independent predictors of DAS28–3 remission at 12 mo were lower baseline DAS28–3 (odds ratio 0.6, 95% confidence interval 0.4–0.7, P P =0.048). Conclusions Three out of every four dmard-naive early RA patients are in remission in Finland after 1 year of diagnosis. High remission rates were achieved with use of csDMARDs in combinations for majority of patients. Treatment with triple therapy is a predictor of DAS28–3 remission also in real-life rheumatology settings. References Mottonen T, Hannonen P, Leirisalo-Repo M, Nissila M, Kautiainen H, Korpela M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: A randomised trial. FIN-RACo trial group. Lancet 1999; 353:1568–73 Leirisalo-Repo M, Kautiainen H, Laasonen L, Korpela M, Kauppi MJ, Kaipiainen-Seppanen O, et al. Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study). Ann Rheum Dis 2013;72:851–7 Acknowledgement We would like to thank study nurses. This study was supported by Pfizer. Disclosure of Interest None declared

Background Efficacy of Tumor Necrosis Factor (TNF)-inhibitors in treatment of rheumatoid arthritis (RA) measured in randomized controlled trials (RCTs) may not be fully generalizable to routine care owing to the stringent inclusion criteria [1]. Objectives The objective of this study was to observe the effectiveness of TNF-inhibitors in Finland and to assess the real-world patients9 potential eligibility for the RCTs. Methods RA patients starting a TNF-inhibitor as their first, second or third biologic treatment between 2004 and 2014 were identified from the National Register for Biologic Treatment in Finland (ROB-FIN), which is an observational cohort study. Effectiveness was measured using the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria and as the proportion of patients reaching Disease Activity Score 28 (DAS28) remission. Logistic regression was employed to identify any predictors of achieving EULAR response. The patients9 baseline characteristics were compared against the inclusion criteria of 28 RCTs identified from two systematic reviews [2,3]. Treatment responses measured in the RCTs were compared to those achieved by routine care patients either eligible or not eligible for the same RCTs. Results Of the 4067 TNF-inhibitor treatment periods, 2259 periods from 1899 patients with valid baseline visit were included in this study. The included patients were predominantly female (73%) with a median age of 55. Adalimumab, etanercept infliximab, golimumab and certolizumab pegol accounted for 41%, 40%, 9.7%, 5.1% and 4.6% of the medication periods, respectively. Moderate and good EULAR responses at 6 months were achieved by 69% and 40% of the users of the first biologic drug, respectively. ACR20, ACR50 and ACR70 responses were reached by 47%, 25% and 13%, respectively. DAS28 remission was reached by 45%. Concomitant use of methotrexate (MTX) was associated with higher odds of achieving at least moderate EULAR response (odds ratio 1.8, 95% confidence interval 1.1– 3.0) as compared to TNF-inhibitor monotherapy. Golimumab and certolizumab pegol were possibly more effective than infliximab, depending on whether the discontinuers were included in the analysis or not. Only 3.8% to 50% of the patients would have been eligible for the included RCTs. The eligible patients had generally better ACR50 responses as compared to the non-eligible ones. Conclusions Different TNF-inhibitors were mostly equipotent in routine clinical practice, but the use of MTX co-therapy had a major influence on treatment response. The efficacy of TNF-inhibitors measured in RCTs cannot be directly generalized into Finnish routine healthcare. References Zink A et al. Arthritis Rheum 2006;54:3399–407. Nam JL et al. Ann Rheum Dis 2010;69:976–86. Nam JL et al. Ann Rheum Dis 2014;73:516–28. Acknowledgement ROB-FIN has received financial support from the following pharmaceutical companies: Abbvie, MSD, Pfizer and Roche Disclosure of Interest None declared

Background and objectivesFive-tumour necrosis factor (TNF)-blockers (infliximab, etanercept, adalimumab, certolizumab pegol and golimumab) are available for treatment of rheumatoid arthritis. Only few clinical trials compare one TNF-blocker to another. Hence, a systematic review is required to indirectly compare the substances. The aim of our study is to estimate the efficacy and the safety of TNF-blockers in the treatment of rheumatoid arthritis (RA) and indirectly compare all five currently available blockers by combining the results from included randomized clinical trials (RCT).MethodsA systematic literature review was conducted using databases including: MEDLINE, SCOPUS (including EMBASE), Cochrane library and electronic search alerts. Only articles reporting double-blind RCTs of TNF-blockers vs. placebo, with or without concomitant methotrexate (MTX), in treatment of RA were selected. Data collected were information of patients, interventions, controls, outcomes, study methods and eventual sources of bias.ResultsForty-one articles reporting on 26 RCTs were included in the systematic review and meta-analysis. Five RCTs studied infliximab, seven etanercept, eight adalimumab, three golimumab and three certolizumab. TNF-blockers were more efficacious than placebo at all time points but were comparable to MTX. TNF-blocker and MTX combination was superior to either MTX or TNF-blocker alone. Increasing doses did not improve the efficacy. TNF-blockers were relatively safe compared to either MTX or placebo.ConclusionsNo single substance clearly rose above others in efficacy, but the results of the safety analyses suggest that etanercept might be the safest alternative. Interestingly, MTX performs nearly identically considering both efficacy and safety aspects with a margin of costs.

Learning to program should include learning about proper software testing. Some automatic assessment systems, e.g. Web-CAT, allow assessing student-generated test suites using coverage metrics. While this encourages testing, we have observed that sometimes students can get rewarded from high coverage although their tests are of poor quality. Exploring alternative methods of assessment, we have tested mutation analysis to evaluate students' solutions. Initial results from applying mutation analysis to real course submissions indicate that mutation analysis could be used to fix some problems of code coverage in the assessment. Combining both metrics is likely to give more accurate feedback.

Biological drugs are used in the treatment of active inflammatory athritides refractory to conventional treatment. Data from the Finnish registry of biological treatment (ROB-FIN) indicates that the effectiveness of the biologicals in clinical practice corresponds to or even excels that of randomized controlled clinical trials, and seems to endure in patients continuing treatment. About one-fifth of rheumatoid arthritis patients discontinue treatment due to lack of effectiveness, and one-tenth due to adverse events. Serious adverse events were seen in 2.5% of all patients. In the future electronic follow-up, pharmacogenetics, and biomarker research may help to better optimize treatment individually.

Background In previous observational studies of TNF-inhibitors, the proportion of patients achieving sufficient clinical response (BASDAI 50) after six months of treatment onset has ranged from 52% to 63% while 26% to 37% have discontinued the treatment within 24 months [1–3]. Objectives The aim of this research was to describe the effectiveness and drug survival of TNF-inhibitors in the treatment of ankylosing spondylitis (AS) in Finland and to analyze the effect of concomitant treatment with conventional Disease-Modifying Anti-Rheumatic Drugs. Methods AS patients enrolled in the National Register for Biologic Treatment in Finland (ROB-FIN) starting their first TNF-inhibitor treatment between July 2004 and December 2011 were included. Treatment response was measured as an improvement of 50% (or 20 mm) after 6 months of treatment onset compared to the baseline BASDAI score. Treatment effectiveness and 2 year drug survival were modelled with logistic regression and time-dependent cox-proportional hazard models, respectively. The results are reported either as Odds Ratios (OR) or Hazard Ratios (HR) where appropriate. Results The study comprised 543 patients, of which 123 also commenced a second TNF-inhibitor during the follow-up. Treatment was discontinued within 24 months by 24% and 28% of the users of the first and the second TNF-inhibitors, respectively. BASDAI50 response at 6 months was achieved by 52% and 25% of the users of the first and the second TNF-inhibitors, respectively. Logistic regression analyses revealed no statistically significant differences between TNF-inhibitors or the use of concomitant cDMARDs. Etanercept (HR 0.48, 95% CI 0.31-0.74) and adalimumab (HR 0.52 95% CI 0.30-0.91) were associated with better drug survival in comparison to infliximab. Also, sulfasalazine (HR 0.70 95% CI 0.49-0.99) decreased the hazard for treatment discontinuation. Conclusions TNF-inhibitors proved equipotent in the treatment of AS, however etanercept and adalimumab were found superior to infliximab in drug survival. Concomitant use of sulfasalazine reduced the hazard for treatment discontinuation possibly by providing a synergistic effectiveness benefit. References Lord P a C, Farragher TM, Lunt M, et al. Predictors of response to anti-TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register. Rheumatology 2010;49:563–70. Glintborg B, Ostergaard M, Krogh NS, et al. Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor: results from 8 years9 surveillance in the Danish nationwide DANBIO registry. Ann Rheum Dis 2010;69:2002–8. Kristensen LE, Karlsson J a, Englund M, et al. Presence of peripheral arthritis and male sex predicting continuation of anti-tumor necrosis factor therapy in ankylosing spondylitis: an observational prospective cohort study from the South Swedish Arthritis Treatment Group Register. Arthritis Care Res 2010;62:1362–9. Acknowledgements We thank all Finnish rheumatologists for their efforts in the data collection and Pfizer for supporting the study. Disclosure of Interest None declared

Background and Objectives Economic evaluations provide information to aid the optimal utilization of limited healthcare resources. Costs of biologics for Rheumatoid arthritis (RA) are remarkably high, which makes these agents an important target for economic evaluations. This systematic review aims to identify existing studies examining the cost-effectiveness of biologics for RA, assess their quality and report their results systematically. Methods A literature search covering Medline, Scopus, Cochrane library, ACP Journal club and Web of Science was performed in March 2013. The cost-utility analyses (CUAs) of one or more available biological drugs for the treatment of RA in adults were included. Two independent investigators systematically collected information and assessed the quality of the studies. To enable the comparison of the results, all costs were converted to 2013 euro. Results Of the 4890 references found in the literature search, 41 CUAs were included in the current systematic review. While considering only direct costs, the incremental cost-effectiveness ratio (ICER) of the tumor necrosis factor inhibitors (TNFi) ranged from 39,000 to 1 273,000 (sic)/quality adjusted life year (QALY) gained in comparison to conventional disease-modifying antirheumatic drugs (cDMARDs) in cDMARD naive patients. Among patients with an insufficient response to cDMARDs, biologics were associated with ICERs ranging from 12,000 to 708,000 (sic)/QALY. Rituximab was found to be the most cost-effective alternative compared to other biologics among the patients with an insufficient response to TNFi. Conclusions When 35,000 (sic)/QALY is considered as a threshold for the ICER, TNFis do not seem to be cost-effective among cDMARD naive patients and patients with an insufficient response to cDMARDs. With thresholds of 50,000 to 100,000 (sic)/QALY biologics might be cost-effective among patients with an inadequate response to cDMARDs. Standardization of multiattribute utility instruments and a validated standard conversion method for missing utility measures would enable better comparison between CUAs.

Background Cost-effectiveness studies provide valuable information on the costs and benefits of the treatments. This information is needed to guide the optimal utilization of limited healthcare resources. Biological drugs for Rheumatoid arthritis (RA) are expensive, yet have great potential to improve patients9 quality of life. Therefore they are an important target for economic evaluation. Objectives The aim of this systematic review is to identify existing studies examining the cost-effectiveness of biologics for RA, assess their quality and report their results systematically. Methods The literature search covering Medline, Scopus, Cochrane library, ACP Journal club and Web of Science was performed in March 2013. The cost-utility analyses of one or more available biological drugs for the treatment of RA in adults were included in the current review. The information on patients, treatments, study design and outcomes were collected using a standardized data collection form. The quality of the studies was assessed using previously published checklists. The results of included studies were stratified by the patients9 previous treatments. Results Of the 4890 references found in the literature search, 38 cost-utility analyses were included in the current systematic review. Thirty-four of the included studies used a modelling approach, while remaining four were empiric studies. The incremental cost-effectiveness ratio (ICER) of the tumor necrosis factor (TNF) blockers ranged from 13,500 to 772,000 €/quality adjusted life year (QALY) in comparison to conventional disease modifying anti rheumatic drugs (cDMARD) in patients with no previous treatment with cDMARDs. Among patients with an insufficient response to cDMARDs, TNF blockers were associated with ICERs ranging from 6,700 to 317,000 €/QALY. Rituximab was found to be the most cost-effective alternative in contrast to other biologics among the patients with an insufficient response to TNF blockers. Conclusions Considering 50,000 €/QALY as an acceptable threshold for the ICER, TNF blockers are unlikely to be cost-effective among patients naive to cDMARDs. Meanwhile, among patients with an insufficient response to cDMARDs they might be cost-effective. Heterogeneity in study designs was reflected in the results and made the comparison of studies difficult. The quality assessment revealed various types of biases in the included studies, potentially compromising the validity of their results. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3110

Background While randomized clinical trials have not showed an increased risk for serious infections among TNF-blocker users in comparison to methotrexate, we sought to confirm the results in Finnish routine care [1]. Objectives The objective of the study was to investigate the incidence of serious infections and malignancies among patients with rheumatoid arthritis (RA) using either TNF-blockers, rituximab or conventional disease modifying anti-rheumatic drugs (cDMARD). Methods Study protocol restricted inclusion to the current users of infliximab, etanercept, adalimumab or rituximab. Additionally, biologic-naive cDMARD users were recruited as a control group. Furthermore, treatments prior to the first recorded out-patient specialized care visit were excluded from the analyses. The follow-up time included a six month lag-time to capture adverse events that occur after discontinuation but may have been due to the exposure. The study population was identified from the National Register of biological treatment in Finland (ROB-FIN) and from the hospital records of Jyvaskyla Central Hospital, the latter providing all the cDMARD patients. Records on serious infections and malignancies were retrieved from the National Hospital Discharge Register and the National Cancer Register, respectively. Data from different registers were merged on the patient level using unique social security numbers. The results are presented as counts, incidence rates per 1000 patient-years (IR) and adjusted hazard ratios (HR) along with their respective 95% confidence intervals. The confounding factors included in the model comprised age, sex, disease activity, time from diagnosis, use of cortisone as well as prior infections and malignancies. Results The study comprised 3,542 patients accumulating 11,337 patient years, including switchers. Between 1999 and 2011 there were 100 (IR 31, 25-38), 179 (IR 24, 21-28; HR 0.9, 0.6-1.3) and 26 (IR 35, 23-51; HR 0.8, 0.4-1.5) serious infections in the DMARD, TNF-blocker and rituximab groups, respectively. The most common serious infections included erysipelas, sepsis, gastroenteritis, bronchitis along with tuberculosis. The results for new-onset malignancies among cDMARD, TNF-blocker and rituximab groups were 39 (IR 12, 9-17), 45 (IR 6, 4-8; HR 1.2, 0.67-2.4) and 7 (IR 9, 4-19; HR 0.7, 0.2-3.0), respectively. Conclusions Nor the unadjusted or adjusted results found evidence of increased risk for serious infections or malignancies among TNF-blocker or rituximab users compared to the cDMARD users. References Aaltonen KJ, Virkki LM, Malmivaara A, et al. Systematic Review and Meta-Analysis of the Efficacy and Safety of Existing TNF Blocking Agents in Treatment of Rheumatoid Arthritis. PLoS One 2012;7:e30275. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.2568

Background Traditionally, only few clinics have participated in reporting results of usual care of patients with Rheumatoid Arthritis (RA). Routine patient monitoring has become more common, which enables collaborative projects to report outcomes of patients with RA. In Finland, a nation-wide review of patients with RA has been missing until to date. Objectives The objective of the study was to conduct a cross-sectional overview on the demographics, disease activity and medical treatment of patients with RA in outpatient specialized healthcare in Finland. Methods Consecutive patients from participating centers were enrolled to the study. The data to be collected comprised demographic, disease and treatment-related variables as well as patient reported outcomes. The data were collected using either purpose-made data collection form or alternatively, GoTreatIt- patient monitoring software. The data were analyzed in SPSS 20 statistical software. Results Between November 2011 and May 2012, 890 patients with RA were enrolled from 14 sites. Percentage of women was 77% while mean age and time from diagnosis were 58.4 (SD 13.8) and 11.6 (SD 11.2) years, respectively. DAS28 values ranged from 0.28 to 6.61 (median 2.55) with 52% and 70% of patients reaching remission and low disease activity, respectively. Meanwhile, according to the ACR/EULAR 2011 remission criteria the proportions of patients in remission were 26% (Boolean) and 28% (SDAI). Rheumatoid factor and CCP-antibodies were evident in 70% and 63% of patients, respectively. Mean HAQ score was 0.87 (SD 0.76) Conventional disease-modifying anti-rheumatic drugs (DMARD) were used by 91% of patients. A triple therapy of methotrexate (MTX), hydroxychloroquine and sulfasalazine was used by 15%, other MTX-based combination by 30%, MTX alone by 20% and other DMARDs alone or in combination by 26% of patients. In addition, corticosteroids and biologics were taken by 58% and 21% of patients, respectively. Mean weekly dose of methotrexate was 17.7mg (SD 5.4) while mean daily dose of prednisolone was 5.6mg (SD 2.8). Of the 184 biologic drug users 18% were not using DMARDs concomitantly. The most prevalent biologic drugs were etanercept (34%), rituximab (19%), adalimumab (16%) and infliximab (11%). Mean time from diagnosis to initiation of the first biologic treatment was 11.4 years (SD 10.0). A comparison between hospital districts revealed some differences in disease activity, which may however, have been confounded by heterogeneity in patient demographics and serologic status. There were differences in the proportion of patients on biologic drugs as well as whether intravenously or subcutaneously administered biologics were preferred. Conclusions Our cross sectional review of patients with RA revealed that >50% of patients were in DAS28-remission and 70% had low disease activity. This observation appeared generalizable among 14 Finnish rheumatology clinics although biologic drugs were only used by 21% of patients. Future prospectives would include similar reviews in other countries to evaluate global generalizability of our results. Disclosure of Interest None Declared