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Appendix F. Abstracts presented in international scientific meetings

2015. Alpizar-Rodriguez D, Muller R, Möller B, Dudler J, Ciurea A, Zufferey P, Kyburz D, Walker UA, Von Mühlenen I, Cornelis F, Bas S, Roux-Lombard P, Gabay C, Finkch A. Female reproductive factors and the development of anti-citrullinated protein antibodies in women at risk of rheumatoid arthritis. Abstract No. AB025. Ann Rheum Dis. 2015; 74 suppl. 2:975.

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Scientific Abstracts 975

where its physiopathology is based on immunological activity. It has been determined that an early therapy with Disease-Modifying Antirheumatic Drugs (DMARDs) stops the progression of this disease. One of the main limitations to achieve this objective is guarantee compliance to DMARDs. Several methods have been designed to measure compliance such as CQR that provides quick and concise information about medication compliance.

Objectives: To develop an initial linguistic and psychometric validation of the CQR questionnaire in patients with RA.

Methods: A validation study was conducted at San Ignacio University Hospital.

Steps suggested by ISPOR Task Force for Translation and Cultural Adaptation were followed, and a final Spanish version for Colombia was created with semantic and content equivalence to the original version. Data collection was performed in four outpatient rheumatology wards. The data collection form completed by the patients included demographic data, CQR19, analog scale of compliance, adverse effects associated with the medication; while doctors registered DAS-28, rheumatoid factor, anti-citrulline antibodies and current treatment. Psychometric validation was evaluated from a hypothesis of correlation between compliance (CQR score) and the level of activity of the disease (DAS-28). The association between compliance, the presence of adverse events, and the amount of medication was also evaluated.

Results: CQR19 was completed by 233 patients with RA diagnosis (Female 75.1%) taking some type of pharmaceutical treatment (single or combined), with a mean of 11.3 years (SD 9.6) into the disease. Correlation between CQR19 score and DAS-28 activity categories was -0.64 (95% CI: -0.71to-0.56). Despite this result, correlation between CQR19 categories [satisfactory compliance (>80%) and unsatisfactory compliance ( 80%)] and DAS-28 was -0.16 (95% CI: -0.28 to -0.03). 97.8% of the patients were classified as satisfactory compliance. All analyses were conducted with Spearman’s rank correlation coefficient based on Fisher transformation. Exploratory analysis showed that association between CQR19 score and adverse events was -0.05 (95% CI: -0.18to0.08), while the association between CQR19 score and the amount of medication was -0.34 (95%

CI: -0.45to-0.22).

Conclusions: CQR19 score relates to DAS-28 categories activity indicating that patients with less activity have higher compliance scores. However, this relationship was not evident when applying the compliance categories established by the CQR19 authors (compliance limit of 80%). Validations of CQR19 scores as a measure of compliance do not allow using this instrument in our local clinical practice in a regular basis. Further studies are necessary to evaluate the ability of CQR19 scores to indicate compliance to the treatment beyond just taking the medication in patients with RA. We suggest exploring other sources of evidence to validate this questionnaire.

References:

[1] De.Klerk E, et al. The compliance-questionnaire-rheumatology compared with electronic medication event monitoring: a validation study. J. Rheumatol. 30, 2469–2475 (2003).

Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2015-eular.5711

WRIST ULTRASOUND BETTER CORRELATES WITH DISEASE ACTIVITY SCORE (DAS28) IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH BIOLOGICS

D. Opris, A. Borangiu, T. Gudu, I. Saulescu, L. Groseanu, D. Predeteanu, R. Ionescu. UMF Carol Davila, Sf.Maria Clinical Hospital, Bucharest, Romania Objectives: To assess which particular joint ultrasound (US) evaluation better correlate with disease activity based on DAS28 in rheumatoid arthritis (RA) patients treated with biologics.

Methods: Consecutive RA patients on stable biologic treatment for more than 6 months were evaluated. Clinical and US evaluation were performed by two independent assessors, the same day as all laboratory tests. The scanning technique and the settings of the machine (ESAOTE MY LAB70, 15 MHz linear probe) were the same for all the patients. Examinations were perform by a trained ultrasonografer who was blinded to all clinical evaluations. US of both hands (dorsal wrist, 2nd to 5th volar metacarpophalangeal and 2nd to 4th volar proximal interphalangeal) was done. Synovial hypertrophy and power Doppler (PD) signal were scored (grade 0–3). Synovial hypertrophy >2 plus power Doppler signal was classified as active synovitis. Based on DAS284v(ESR) patients were split in 2 groups: remission and non-remission.

Results: One hundred and six patients were evaluated. Most of them (84%) were females, mean age group 58.72 (11.49) years, mean disease duration

13.48 (7.4) years. Regarding the treatment, 87.7% had a DMARD associated to the biologic: 49.1% (52) patients were treated with rituximab, 27.35% (29) with etanercept,19.9% (19) with adalimumab, 9.33% (9) with infliximab. Mean DAS28 ESR was 3.14, with 36.8% of patients being on remission. We found a significant statistical difference (p=0.005) between active synovitis score in active disease patients (82.05% of them heaving active synovitis) versus 56.41%

synovitis in remission patients. Statistical significance was also found regarding inflammation markers, PD joint number, PD total score, but not regarding Grey Scale (GS) number and total score (see table). When every joint was evaluated separately, statistically significance was found only between wrists and PD: right wrist (p=0.01) and left wrist (p=0.002), but not for GS (p=0.181 and 0.337).

Conclusions: Active synovitis score, total PD joint number and total PD score correlates with DAS284vESR in rheumatoid arthritis patients treated with biologics.

Both wrist US evaluation seems to be the most accurate in identifiing disease activity.

Acknowledgements: This paper is partially supported by the Sectoral Operational Program Human Resources Development, financed from the European Social Found POSDRU/159/1.5/S/137390.

Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2015-eular.5696

FEMALE REPRODUCTIVE FACTORS AND THE DEVELOPMENT OF ANTI-CITRULLINATED PROTEIN ANTIBODIES IN WOMEN AT RISK OF RHEUMATOID ARTHRITIS

D. Alpizar-Rodriguez ¹, R.B. Mueller ², B. Möller ³, J. Dudler ⁴, A. Ciurea ⁵, P. Zufferey ⁶, D. Kyburz ⁷, U.A. Walker ⁷, I. Von Mühlenen ⁷, F. Cornelis ⁸, S. Bas ¹, P. Roux-Lombard ¹, C. Gabay ¹, A. Finckh ¹. ¹HUG, Geneva; ²KSSG, St Gallen;

3Inselspital, Bern; ⁴HFR, Fribourg; ⁵USZ, Zurich; ⁶CHUV, Lausanne; ⁷USB, Basel, Switzerland; ⁸GenHotel-Auvergne, Clermont-Ferrand, France Background: The etiopathogenesis of rheumatoid arthritis (RA) is viewed as a multi-step process whereby environmental factors induce pathologic activation of the immune system that eventually leads to clinical onset of RA in genetically susceptible individuals. Systemic autoimmunity associated with RA is one of the phases preceding the development of the disease. The role of female hormonal factors is controversial and their relation in the transition to systemic autoimmunity has not been studied. Recently, observational studies have suggested differences in the role of female reproductive factors between anti-citrullinated protein antibodies (ACPA) negative and positive RA.

Objectives: To analyze the association between female reproductive factors and the development of systemic autoimmunity associated with RA.

Methods: This is a prospective cohort study of first degree relatives (FDRs) of patients with established RA. Only individuals without clinical evidence of RA are enrolled and followed-up yearly. We included in this analysis only female participants with available ACPA status (anti-CCP 2.0 or 3.1) and full information on reproductive factors. The outcome of interest was the presence of ACPA. The predictor of interest was the cumulative lifetime estrogen (CLE) exposure as previously described (1). This composite score integrates a history of menarche 10 years, 3 or more pregnancies, hysterectomy, hormonal contraceptive or replacement therapy and age at menopause 53 years. Based on the CLE score, women were categorized as being low, moderate or high estrogen exposed. We used logistic regression to analyze univariate and multivariate associations between ACPA positive status, CLE exposure and other specific reproductive factors.

Results: A total of 583 women FDRs were analyzed, of which 93 (16%) were ACPA-positive. Characteristics were balanced between ACPA positive and negative FDRs with a mean age of 48.3 and 44.9 years and heavy tobacco smoking (>10 pack-years) in 45 and 46% respectively. Positive shared epitope (SE) in 8 and 10% and positive rheumatoid factor in 17% of subjects in both groups. In a multivariate adjusted analysis, low CLE exposure was associated with ACPA positivity (OR 1.88, p=0.03). High CLE exposure was also numerically associated with an increased risk of ACPA (OR 1.57, p=0.36), even though not significantly. We found no significant association between ACPA positivity and SE, ever smoking, obesity, breastfeeding or postmenopausal status.

Conclusions: In women at increased risk of RA, the development of ACPAs was found to be associated with low lifetime exposure to estrogens, however high lifetime estrogen exposure also tended to increase the risk of ACPAs positivity, suggesting a non-linear association between estrogenic exposure and the development of ACPAs. We plan to replicate these findings in a separate cohort.

If this non-linear association was confirmed it could explain some discordant findings in the literature.

References:

[1] Gatto NM et al. Parkinsonism Relat Disord 2014; 20(11):1149-56.

Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2015-eular.3058 AB0250

AB0251

DAS 28 remission group (SD) DAS 28 non-remission group (SD) p

Tender joint count 0.00 (0.00) 2.06 (2.54) <0.001

Active synovitis 56.41% 82.08% 0.005

2016 Alpizar-Rodriguez D, Brulhart L, Muller R, Möller B, Dudler J, Ciurea A, Walker U, Von Mühlenen I, Kyburz D, Zufferey P, Mahler M, Bas S. Gascon D, Lamacchia C, Roux-Lombard P, Lauper K, Nissen M, Courvoisier D, Gabay C, Finkch A. Predictors for the development of anti-citrullinated protein antibodies in individuals genetically at risk for rheumatoid arthritis. Abstract No. FRI0071. Ann Rheum Dis. 2016;75:suppl2:452.

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452 Friday, 10 June 2016 Scientific Abstracts

MSD, Pfizer, Abbott, UCB, Roche, C. Turesson Consultant for: Abbvie, BMS, Janssen, MSD, Pfizer, Roche, UCB, X. Mariette: None declared, D. Choquette:

None declared, A. Finckh Consultant for: Abbvie, BMS, MSD, Pfizer, Roche DOI: 10.1136/annrheumdis-2016-eular.3536

PREDICTORS FOR THE DEVELOPMENT OF

ANTI-CITRULLINATED PROTEIN ANTIBODIES IN INDIVIDUALS GENETICALLY AT RISK FOR RHEUMATOID ARTHRITIS D. Alpizar-Rodriguez ¹, L. Brulhart ¹, R. Müller ², B. Möller ³, J. Dudler ⁴, A. Ciurea ⁵, U. Walker ⁶, I. Von Mühlenen ⁶, D. Kyburz ⁶, P. Zufferey ⁷, M. Mahler ⁸, S. Bas ¹, D. Gascon ¹, C. Lamacchia ¹, P. Roux-Lombard ¹, K. Lauper ¹, M. Nissen ¹, D. Courvoisier ¹, C. Gabay ¹, A. Finckh ¹. ¹HUG, Geneve; ²KSSG, St Gallen; ³Inselspital, Bern; ⁴HFR, Fribourg; ⁵USZ, Zurich; ⁶USB, Basel; ⁷CHUV, Lausanne, Switzerland; ⁸Inova Diagnostics, San Diego, CA, United States Background: In genetically susceptible individuals, environmental factors induce a pathological activation of the immune system that may eventually lead to systemic autoimmunity and subsequent clinical manifestations. Different risk factors may be relevant for the development of this systemic autoimmunity, representing one of the phases preceding the onset of rheumatoid arthritis (RA) (1).

Objectives: To identify predictors for the development of systemic autoimmunity associated with RA in individuals genetically at increased risk.

Methods: This is an ongoing prospective cohort study of individuals at increased risk of developing RA, namely first degree relatives of patients with autoimmune diseases (FDRs). Individuals without clinical evidence of RA were enrolled and followed-up yearly. We included all individuals with available anti-citrullinated protein antibodies (ACPA) status (anti-CCP 2, 3.0, or 3.1). We used logistic regression to analyze univariable and multivariable associations between ACPA positivity and putative risk factors or symptoms, including the Connective Tissue Disease Screening Questionnaire (CSQ), 3 or more positive responses represented possible RA (2).

Results: A total of 1064 of FDRs were analyzed, of which 57 (5%) were ACPA-positive. FDRs had a median age of 45 (interquartile range (IQR): 34–56) years, 76% were female, 25% had at least one self-reported episode of joint swelling, however on examination only 12% had 1 swollen joint (Table 1). In univariable analyses, ACPA-positivity was associated with older age, female sex, tender joints (self reported, 1 on examination and mean count), mean swollen joint count, CSQ score and self-reported symptoms associated with possible RA by CSQ. Other variables such as tobacco smoking, alcohol consumption, obesity or tooth loss were not significantly associated with ACPA status. In women, ACPA-positivity was significantly associated with age (OR: 1.1, 95%CI: 1.0–1.1), but not in men (OR: 1.0, 95%CI: 0.9–1.1). In the multivariable adjusted analysis, older age and self-reported symptoms associated with possible RA by CSQ remained independently associated with ACPA positivity. Female sex and tobacco smoking ever had a strong but not significant association.

Conclusions: In individuals at high risk for RA, the development of ACPAs was associated with older age and self-reported symptoms related with possible RA.

We found a trend for an association between female sex and tobacco smoking with ACPA positivity, which did however not reach statistical significance. These findings suggest similar risk factors for the development of ACPAs and for classifiable RA, suggesting that the development of ACPAs is a valid proxy for RA development.

References:

[1] Gerlag DM et al. Ann Rheum Dis. 2012; 71(5): 638–41.

[2] Karlson EW, et al. Ann Epidemiol 1995;5:297–302.

Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2016-eular.2652

EARLY DETECTION OF INFLAMMATORY ARTHRITIS: THE ROLE OF MUSCULOSKELETAL SYMPTOMS, INFECTIONS AND RHEUMATOID ARTHRITIS-RELATED COMORBIDITIES IN PRIMARY CARE

M.H.V. Beers-Tas ¹, M.M. Nielen ², J.C. Korevaar ², D.V. Schaardenburg ¹.

1Amsterdam Rheumatology & immunology Center, Amsterdam; ²Nivel, Utrecht, Netherlands

Background: Rheumatoid arthritis is characterized by clinically apparent inflam- matory arthritis (IA). A preclinical phase has been recognized in which symptoms arise and ambulatory care utilization increases. However, information on location and timing of symptoms before IA diagnosis is still largely lacking.

Objectives: The present study was undertaken to identify pathogenetic clues to the development of IA and to assist early identification of future IA patients with a focus on musculoskeletal symptoms, infections and chronic comorbidities.

Methods: We conducted a nested case-control study using data from electronic medical records of general practitioners, participating in NIVEL Primary Care Database, to evaluate timing and numbers of visits for symptoms linked to above mentioned groups before a diagnosis of IA. Cases were adults who received a newly diagnosis of IA between 2012 and 2014, in total 2772. Retrospective follow-up had a median of 3.4 years (range 1–9). Controls were matched 1:2 on age, gender, general practice and retrospective duration of follow-up. We studied a total of 192 different symptoms or (chronic) diseases using the International Classification of Primary Care (ICPC-1) coding system. The frequency of primary care visits between the IA patients and controls were compared using logistic regression in different time periods before date of diagnosis. To investigate which of the individual symptoms or diseases were seen often, chisquare tests (chi2) were performed to evaluate the difference in frequency of these symptoms in the IA-patients compared to the controls.

Results: The consultation rate for musculoskeletal symptoms was increased in IA patients within the last 1.5 years before diagnosis with odds ratios (ORs) of 1.8 (confidence interval; CI: 1.6–2.1, p-value<0.05), 1.4 (CI 1.2–1.6, p<0,05) and 1.3 (CI 1.1–1.5, p<0.05), respectively, at 6, 12 and 18 months before diagnosis.

For infections, the consultation rate was significantly higher 6 and 18 months prior to diagnosis (OR=1.2; both CI: 1.1–1.4, p-value<0.05). Finally, for IA-related disease and other chronic diseases a significant difference was observed only 3 months before diagnosis with ORs of 1.2 (CI 1.02–1.3, p<0.05) and 1.3 (CI 1.1–1.5, p<0.05) respectively. All ORs are corrected for age and gender.

Important contributors to the above mentioned significance levels were presence of shoulder complaints (16.1% in the IA-patients versus 9.6% in the controls; chi2 73.9, p<0.001), hand/finger complaints syndrome (12.2% versus 5.6%; chi2 112.5, p<0.001), carpal tunnel syndrome (5% versus 2.5%; chi2 37.1, p<0.001) and foot/toe complaints (15.2% versus 9.2%; chi2 67.0, p<0.001). Numbers of individual infections were too small to find any statistical differences between the groups.

Conclusions: We found significantly increased consultation rates in general practice for musculoskeletal symptoms and infectious diseases prior to the diagnosis of IA. This diverging trend started 4–6 years before diagnosis, but becomes statistically significant around 1.5 years preceding diagnosis. IA-related comorbidities and chronic diseases also show this trend, however this did not reach significance until nearly at the IA date. Possibly, these symptoms can be used to develop methods for earlier detection of IA in general practice.

Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2016-eular.2354 FRI0071

FRI0072

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2016 Alpizar-Rodriguez D, Muller R, Möller B, Dudler J, Ciurea A, Von Mühlenen I, Kyburz D, Zufferey P, Gascon D, Lamacchia C, Roux-Lombard P, Lauper K, Courvoisier D, Gabay C, Finckh A. Menopause is a predictor for the development of anti-citrullinated protein antibodies in women at risk for rheumatoid arthritis. Abstract No. AB0178. Ann Rheum Dis. 2016;75:suppl2:957-58

Scientific Abstracts 957

ACPA-positive RA (<36 months duration) were enrolled. After obtaining informed consent, all subjects underwent baseline pulmonary function tests (PFTs), DLCO measurement and cardiopulmonary exercise testing (CPET). A blood sample for the ELISA evaluation of Surfactant protein D (SP-D) serum levels was collected.

Serum levels of SP-D were also measured in 9 healthy control age and sex- matched. Exclusion criteria were: cardiovascular disease, lung disease already known, diabetes, other autoimmune diseases

Results: The cohort consisted of 7 men and 23 women, mean age 48,93 (DS

±12.1). PFTs resulted abnormal only in 2 patients. A DLCO reduction was observed in 54.5% of ACPA-positive subjects without RA, in 60% and in 55.6% of patients with early and established RA, respectively. In RA patients, an inverse correlation between disease duration and ratio of the diffusing capacity to the alveolar volume (DLCO/Va) (r=-0.50; p=0.03) was observed. The exercise tolerance (V’O2 peak) at CPET was reduced in 54.5% of ACPA-positive subjects without RA, in 20% of patients with early RA and in 55.6% of those with established RA. Serum levels SP-D were higher in established RA (p=0.079) and in ACPA-positive subjects and early RA than in healthy control. Interestingly enough, ACPA levels positively correlated (r=0.45; p=0.01) with CPET parameters of ventilatory inefficiency (ratio of the increase in ventilation (V’E) to the increase in CO2 output (V’CO2) at lactic threshold (LT)-V’E/V’CO2@LT), suggesting a ventilation/perfusion mismatch. A negative correlation between ACPA and SP-D levels and CPET metabolic parameters (oxygen uptake (V’O2)) was also observed (SP-D-V’O2@LT/kg r=-0.38 p=0.03 – V’O2@LT/kg-ACPA r=-0.36 p=0.05).

Conclusions: The lung involvement in RA, particularly in the early phases of disease, is often subclinical and baseline PFTs are scarcely informative. Although preliminary, these findings suggest that DLCO, CPET parameters and SP-D can represent early markers of the subclinical lung injury. Additional studies are however needed to clarify lung abnormalities in RA.

References:

[1] Demoruelle et al. Annals of the Rheumatic Diseases 2012 [2] Valesini et al. Autoimmunity Review 2015

Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2016-eular.5712

PATIENT-REPORTED OUTCOME OF UPPER EXTREMITY SURGERY FOR RHEUMATOID ARTHRITIS

D. Kaneda ¹, H. Ohashi ¹, A. Takeshita ¹, M. Horita ¹, T. Machida ¹, R. Nakahara ¹, Y. Nasu ², K. Hashizume ³, K. Nishida ^1,4, T. Ozaki ¹. ¹Department of Orthopaedic Surgery; ²Department of Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; ³Department of Orthopaedic Surgery, Okayama Rosai Hospital; ⁴Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, Okayama, Japan

Background: The goal of treat to target (T2T) is the clinical remission in patients with early disease, but it is difficult to achieve the functional remission. Although patient’s subjective evaluation is important for the assessment of postoperative functions of rheumatoid arthritis (RA) patients, there are few reports examined the patients-reported functions after upper extremity surgery for RA.

Objectives: Between 2011 and 2014, 158 RA patients underwent the surgical treatment on upper extremities, and all patients were available for detailed clinical review over a 1-year follow-up period. There were 144 females and 14 males with a mean age at surgery of 59.7 (range, 18–85) years. The average disease duration at the surgery was 19.6 (range, 1–59) years.

Methods: The clinical outcome of the surgery was assessed by the disease activity (DAS28-CRP), Health Assessment Questionnaire Disability Index (HAQ- DI), Disability of Arm Shoulder and Hand (DASH), Hand20 questionnaire (Hand20). The patients were divided by surgical site into 3 groups (elbow, wrist and finger groups) and by the use of biological disease-modifying anti-rheumatic

drugs (bDMARDs) into 2 groups (bDMARDs and non-bDMARDs groups) to compare and evaluate the outcomes.

Results: The mean of preoperative/postoperative DAS28-CRP, HAQ-DI, DASH and Hand20 were 2.9/2.3, 0.88/0.94, 46.4/39.1 and 59.1/47.6, respectively. All outcomes except for HAQ-DI significantly improved after the surgery. All outcomes improved significantly in the elbow group, but could not reach significant improvement in the finger group. We further examined the postoperative change in each items of DASH and Hand20, and found the significant improvements in items about pain and weakness in elbow group, pain and rotation of forearm in wrist group, and delicate movement and cosmetic factor in finger group. Postoperative DASH and Hand20 scores were tend to improve in the both bDMARDs and non-bDMARDs group.

Conclusions: Our results confirmed the surgery on upper extremity of RA improved

Conclusions: Our results confirmed the surgery on upper extremity of RA improved