Secondary loss of effectiveness among rheumatoid arthritis patients treated with tumour necrosis factor inhibitors

Presentations at the annual meeting of the Finnish Society for Rheumatology, Turku, 26–27 January 2017 Secondary loss of effectiveness among rheumatoid arthritis patients treated with tumour necrosis factor inhibitors K Aaltonen, P Isomäki, J Joensuu, T Sokka, R Peltomaa, L Pirilä, T Varjolahti-Lehtinen, T Uutela, T Malmi, P Ekman, A Kononoff, K Eklund Faculty of Pharmacy, University of Helsinki, Helsinki, Finland, Department of Medicine, Tampere University Hospital, Tampere, Finland, Faculty of Medicine, University of Tampere, Tampere, Finland, Department of Medicine, Jyväskylä Central Hospital, Jyväskylä, Finland, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland, Department of Medicine, Turku University Hospital, Turku, Finland, Department of Medicine, Tampere City Hospital, Tampere, Finland, Department of Medicine, Lapland Central Hospital, Rovaniemi, Finland, Department of Medicine, Seinäjoki Central Hospital, A B C Figure 1. Clinical images of the sclera: (A) injected sclera at presentation; (B) injected sclera at disease flare; (C) normal sclera after tocilizumab therapy. Abstracts 419 www.scandjrheumatol.dk Seinäjoki, Finland, Department of Medicine, Rauma Central Hospital, Rauma, Finland, Department of Medicine, Kuopio University Hospital, Kuopio, Finland, Faculty of Medicine, University of Helsinki, Helsinki, Finland Objective: Treatment response to tumour necrosis factor (TNF) inhibitors may be lost, possibly as a result of the formation of anti-drug antibodies. The objective of this study was to look into secondary loss of effectiveness (SLOE) and the predictors thereof among patients with rheumatoid arthritis (RA). Method: RA patients with primary response to TNF inhibitors [American College of Rheumatology (ACR) 20 or 28-joint Disease Activity Score (DAS28) ≤3.2] were identified from the national register for biologic treatment in Finland (ROB-FIN) and followed for 36 months or until the response was lost. Kaplan–Meier estimators and Cox proportional hazards model were employed in time-to-event analyses. Results: The study comprised 2176 primary responders who were predominantly female, with a median age of 55 years. The probability of experiencing a SLOE within 36 months was 17% and the mean time between achieving and subsequently losing the treatment response was 9.7 months. There was no statistically significant difference in the hazard for SLOE between individual TNF-inhibiting agents. Concomitant use of methotrexate [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.52–1.2] and other conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) (HR 0.81, 95% CI 0.52–1.3) showed a statistically non-significant trend towards protecting against SLOE in comparison to biological monotherapy. Conclusion: According to our results, different TNFinhibiting agents are comparable in relation to the risk for secondary loss of effectiveness. Concomitant therapy with csDMARDs did not protect against loss of effectiveness in a statistically significant manner, but this may have been due to insufficient statistical power. Neutrophil involvement in local tissue reactions of seropositive rheumatoid arthritis S Turunen, J Huhtakangas, T Nousiainen, M Valkealahti, J Melkko, J Risteli, P Lehenkari Department of Anatomy and Cell Biology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland, Division of Rheumatology, Department of Internal Medicine, Oulu University Hospital, Oulu, Finland, Division of Orthopedic Surgery, Oulu University Hospital, Oulu, Finland, Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu and Oulu University Hospital, Oulu, Finland, Department of Clinical Chemistry, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland, Northern Finland Laboratory Center NordLb, Oulu University Hospital, Oulu, Finland Objective: In rheumatoid arthritis (RA), antibodies binding to citrullinated and carbamylated proteins predict a more severe form of disease, but the role in the pathological processes behind the disease induction is not well known. We wanted to determine the biological significance of these post-translational modifications in RA and osteoarthritis (OA) tissue. Method and Results: We analysed citrulline and homocitrulline contents of seropositive and seronegative RA and OA synovial tissues, and found significantly higher citrulline and homocitrulline levels in seropositive RA tissue compared to both seronegative RA and OA. Histologically, these differences were explained by localization of the citrullinating enzymes PAD2, PAD3, and PAD4 in the cells adjacent to necrosis in the knee and metatarsal synovial tissues and rheumatoid nodules in seropositive RA patient tissues. We also found neutrophil myeloperoxidase in the seropositive RA tissue, where necrosis was present. Myeloperoxidase localized in intact neutrophils adjacent to necrotic areas, diffusely in the stroma, and inside the necrotic area, suggesting neutrophil extracellular trap formation. Myeloperoxidase can facilitate homocitrulline formation, so this could explain the differences in homocitrulline contents of the tissues. Conclusion: Seropositive RA inflammatory tissue reactions are different from seronegative RA and OA inflammation in citrulline and homocitrulline formation. The major difference is the higher amount of necrotic tissue in the RA joint. In RA patients, the necrosis inflicts a different neutrophil activation and extracellular matrix modification, which includes citrullination and homocitrullination. We believe that this observation could explain the development of autoantibodies in a novel way. Individuals with low educational level are at a higher risk for rheumatoid arthritis than those with higher education K Puolakka, H Kautiainen Department of Medicine, South Karelia Central Hospital, Lappeenranta, Finland, Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland Objective: Rheumatoid arthritis (RA) is a chronic rheumatic disease with a female preponderance and genetic background. The only well-known modifiable risk factor is tobacco, which causes citrullination of tissues resulting in the formation of anti-citrullinated autoantibodies. These seem to induce the immune disorder in individuals with genetic susceptibility, leading to RA. Other factors in the environment may likewise act as a trigger for immunization, and population-based case–control studies may lead to hypotheses about aetiological factors. Educational level has a multifaceted impact on a person’s lifestyle and health behaviour, including diet, exercise, and the use of tobacco and alcohol. In this study, we compare the distribution of educational level in incident RA patients to that in population controls. 420 Abstracts www.scandjrheumatol.dk Method: All patients with incident RA (identified by ICD codesM05 andM06) from 1 January 2000 to 31December 2014 were gathered from the nationwide special reimbursement register of the Social Insurance Institution. For each case, three controls according to gender, date of birth, and residence were identified from the National Population Register. Data on educational level for these individuals was obtained from Statistics Finland. Results: Men with incident RA more often had lower than mid-level education than population controls, and the difference was the same regardless of rheumatoid factor status (Table). In women, the difference was smaller. Conclusion: Lower education seems to be associated with factors triggering RA. Periodontitis in early and chronic rheumatoid arthritis: a prospective follow-up study in a Finnish population L Äyräväinen, M Leirisalo-Repo, A Kuuliala, K Ahola, R Koivuniemi, JH Meurman, AM Heikkinen Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland, Department of Rheumatology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland, Department of Bacteriology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Objective: To investigate the association between rheumatoid arthritis (RA) and periodontitis, with an emphasis on the role of anti-rheumatic drugs in periodontal health. Method: In this prospective follow-up study, patients with early untreated rheumatoid arthritis (ERA) and chronic active rheumatoid arthritis (CRA) were examined at baseline and 16 months later. Controls were examined once. The study was conducted from September 2005 to May 2014 at Helsinki University Hospital, Finland. Overall, 124 participants were recruited for dental and medical examinations: 53 patients with disease-modifying anti-rheumatic drug (DMARD)-naїve ERA and 28 with CRA with insufficient response to conventional DMARDs. After baseline examination, ERA patients started treatment with synthetic DMARDs and CRA patients with biological DMARDs. Controls were 43 age-, gender-, and community-matched subjects. Outcome measures were degree of periodontitis (defined according to the Centers for Disease Control and Prevention and American Academy of Periodontology), prevalence of periodontal bacteria (from plaque samples), clinical rheumatological status (28-joint Disease Activity Score), function (Health Assessment Questionnaire), and treatment response (European League Against Rheumatism criteria). Results: Moderate periodontitis was present in 67.3% of ERA patients, 64.3% of CRA patients, and 39.5% of controls (p=0.001). Patients with RA had significantly more periodontal findings than controls, recorded with common periodontal indices. At the re-examination, patients with RA still showed poor periodontal health despite DMARD treatment after baseline examination. The prevalence of Porphyromonas gingivalis was higher i