Rheumatoid Arthritis Duration Research Articles

Factors of atherosclerosis progression in rheumatoid arthritis, prospective study data

Abstract Aim of the study Determine in prospective observation study the factors of progression of atherosclerosis in pts with rheumatoid arthritis (RA) during 3 yrs. Matherial and methods This prospective study included 124 patients with RA and suspected ischemic heart disease (IHD), the average age was 58 [52; 63] years. Follow-up period was 3 years (37.5 moths). All RA pts were examined and had treatment, according to European and National guidelines for the diagnosis and treatment of stable CAD (2013) and EULAR for RA (2016). Carotid ultrasound and coronary angiography were also completed. In course of all RA pts the following risk factors were assessed: arterial hypertension (AH), smoking, overweightbody (BMI), heredity for cardiovascular diseases (CVD), diabetes mellitus (DM), dyslipidemia (DLP). The laboratory studies were: CBC and total cholesterol (TC), HDL-C, LDL-C, TG, highly sensitive C-reactive protein (hs-CRP), RA detected activity markers: rheumatoid factor (RF), antibodies to cyclic citrullinated peptide (ACCP), index DAS28. Pro-inflammatory cytokines -interleukin (IL) -1-beta, IL-6, tumor necrosis factor alpha (TNF alpha) were assessed in single RA pts once after 3 years of observation. Results The median duration of RA in inclusion in the study was 11 years, the DAS28 index was 3.8 points (middle degree of activity). DLP was detected in 41% RA pts. DM was in 13% pts. In RA pts, initially atherosclerotic plaques with stenosis of the carotid arteries (CA) 20% or more in 94 pts (77%) were revealed, in 3 of them CA stenosis exceeded 50%. 90 RA pts (72%) were examined again. 21 pts had signs of progressing atherosclerosis marked in CA and/or coronary arteries: 12 (13%) RA patients had only progression of atherosclerosis of CA, 7 (8%) - only progression of atherosclerosis of coronary arteries, 2 (2%) had both progression CA and coronary arteries. There are 2 formed subgroups of RA pts: Gr1 with the progression of atherosclerosis (n=21) and Gr 2 without progression of atherosclerosis (n=69). There are no differences between groups of risk factors of atherosclerosis development age, AH, BMI, lipids,TG, hs CRP, index DAS28. Following rick factors: smoking (n=12 (57%) vs n=21 (30%)), heredity for CVD (n=11 (52%) vs n=17 (25%)), RA duration (13 yrs [10; 18] vs 12 years [6; 18]) were often revealed among pts of Gr 1. All differences p>0.05 Immunological data TNF alfa level, (8,08 [2,3; 8,44] pg/ml vs 1,22 [0,13; 8,00] pg/ml), IL-1β level, 3,97 [3,56; 4,10] pg/ml vs 3,52 [0,30; 4,53] pg/ml, and IL-6 level 3,50 [2,92; 5,76] pg/ml vs 2,52 [0,92; 4,36] pg/ml were significant higher in Gr1 than in Gr2. All differences was p>0.05. Conclusion The progression of atherosclerosis in RA with a low and moderate degree of activity of the disease occurs despite antirheumatic and lipid-lowering therapy. The development of atherosclerosis in this disease is defined by lipid, inflammatory and immunological disorders. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Russion National Cardiology Research Center Ministry of Health of Russion Federation

Factores asociados con fracturas vertebrales asintomáticas en pacientes con artritis reumatoide en un servicio de reumatología de Bogotá (Colombia)

IntroductionIn patients with rheumatoid arthritis (RA), osteoporotic vertebral fractures (VOF) are of multifactorial aetiology. The main mechanism is spontaneous and therefore most are asymptomatic. The presence of VF has an impact on the quality of life of patients, and consequently on morbidity and mortality, therefore it should be systematically evaluated in this population, especially when associated factors have been reported. ObjectivesThe main objective of this study was to identify clinical characteristics for osteoporosis and poor prognosis in rheumatoid arthritis that could be associated with the development of osteoporotic vertebral fractures identified in the lateral chest X-ray of asymptomatic patients with RA. The secondary objectives were to present the frequency, location, and severity of the fractures, as well as the inter and intra-observer correlation, when analysing the radiographs. MethodologyPatients with a diagnosis of RA were included, with a lateral chest X-ray and indication dissimilar to spinal symptoms. The mean age was 58 years (IQR 21-88). Three researchers evaluated 151 images in a sequenced and standardized manner using the Algorithm-Base Qualitative approach (ABQ) and Genant methods. Variables associated with the presence of osteoporosis and poor prognosis in RA were identified. Subsequently, a multivariate analysis was carried out to find an association with the presence of VF in this population. ResultsWe found 39 fractures in 32/151 patients. Identifying multiple fractures in 5 of them. The prevalence of osteoporotic vertebral fractures was 21.2%. The distribution of fractures was mainly at the level of T5, T8 and T9, with a predominance of Genant grade 1 in 46%. In the multivariate analysis, age, duration of RA (mainly greater than 10 years), rheumatoid factor, anti-citrullinated peptide antibodies, DAS28, HAQ, presence of antinuclear antibodies (ANA), smoking and being under treatment for osteoporosis showed a statistically significant association. The interobserver correlation for the ABQ and Genant methods presented a kappa index of.9 and.92, respectively. ConclusionIn patients with RA there is a significant association with the development of VF, independent of the presence of osteoporosis. Furthermore, this research suggests that the presence of some clinical and paraclinical characteristics could be associated with the prevalence of osteoporotic vertebral fractures. Age, duration of arthritis, poor prognostic markers for RA in terms of serology and functionality, as well as being in treatment for osteoporosis had statistical significance of association. This should guide the timely detection of fractures, independent of symptoms, with the respective targeted treatment in this population and thus avoid functional complications and a decrease in quality of life.

A Comparison of Demographics, Disease Activity, Disability, and Treatment Among Rheumatoid Arthritis Patients with and without Osteoporosis.

IntroductionOsteoporosis (OP) is one of the most common comorbidities associated with rheumatoid arthritis (RA). Literatures reported that the risk for developing OP was strongly associated with duration and severity of RA. We aim to elaborate on the consequences of OP on disease activity and management plan in patients with RA.Patients and MethodsA retrospective cohort study recruited 408 patients, including those with RA alone and with RA plus OP. The RA disease activity in the patients was assessed using disease activity score in 28 joints (DAS28-CRP). A statistical analysis was performed to compare data between the two groups of patients and determine any significant risk factor associated with the development of OP in RA patients.ResultsOf 408 patients who were included in this study, 353 patients (86.5%) had only RA, while 55 patients (13.5%) had RA with OP and showed significant difference (P = 0.04) concerning age categories. Patients diagnosed with RA and OP had RA duration longer than RA-only patients (independent t-test, P = 0.01). The two groups had almost similar disease activity at the three clinical visits, as well, had nearly similar disability at their first visit, whereas RA with OP patients had significant greater disability at their 2nd and 3rd visits (independent t-test, P = 0.001). Both groups were treated with the same biologic and non-biologic medication of similar frequency, although RA patients with OP received steroid more frequently than patients had RA only (61.7% vs. 41.7%, chi square test, P = 0.03).ConclusionThere was no significant difference in disease activity at both groups of patients. However, RA with OP group had longer duration of RA, were more frequently treated with steroids, and had greater disability. We recommend physicians focus on controlling RA disease activity, early screening for and treating of OP.

Prediction of sustained biologic and targeted synthetic DMARD-free remission in rheumatoid arthritis patients.

ObjectivesThe aim was to develop a prediction model of sustained remission after cessation of biologic or targeted synthetic DMARD (b/tsDMARD) in RA.MethodsWe conducted an explorative cohort study among b/tsDMARD RA treatment episode courses stopped owing to remission in the Swiss Clinical Quality Management registry (SCQM; 2008–2019). The outcome was sustained b/tsDMARD-free remission of ≥12 months. We applied logistic regression model selection algorithms using stepwise, forward selection, backward selection and penalized regression to identify patient characteristics predictive of sustained b/tsDMARD-free remission. We compared c-statistics corrected for optimism between models. The three models with the highest c-statistics were validated in new SCQM data until 2020 (validation dataset).ResultsWe identified 302 eligible episodes, of which 177 episodes (59%) achieved sustained b/tsDMARD-free remission. Two backward and one forward selection model, with eight, four and seven variables, respectively, obtained the highest c-statistics corrected for optimism of c = 0.72, c = 0.70 and c = 0.69, respectively. In the validation dataset (47 eligible episodes), the models performed with c = 0.99, c = 0.80 and c = 0.74, respectively, and excellent calibration. The best model included the following eight variables (measured at b/tsDMARD stop): RA duration, b/tsDMARD duration, other pain/anti-inflammatory drug use, quality of life (EuroQol), DAS28-ESR score, HAQ score, education, and interactions of RA duration and other pain/anti-inflammatory drug use and of b/tsDMARD duration and HAQ score.ConclusionOur results suggest that models with up to eight unique variables may predict sustained b/tsDMARD-free remission with good efficiency. External validation is warranted.

Osteoporosis risk factors analysis in rheumatoid arthritis patients: data from real practice

Background. Osteoporosis (OP) and its consequences is a pivotal medical and social problem. Rheumatic diseases especially rheumatoid arthritis (RA) is considered a key factor in the development of secondary OP. At the same time, patients with RA also have traditional risk factors (RF) for OP, as well as the adverse effects of drugs on bone metabolism. Consideration of the full spectrum in each patient with RA plays an important role in the individualized assessment of the risk of OP and the rational management.The aim. To analyze the most significant RF of OP in a cohort of patients with verified RA observed by primary care specialists.Materials and methods. Medical cards of 100 patients with determined RA (ACR / EULAR criteria) who were observed at out-patient clinics were studied. Along with the analysis of the clinical manifestations of RA, the registration of OP RF, both traditional and disease-related, was carried out with an analysis of the prevalence of RF in the investigated cohort.Results. The RA cohort under study was dominated by patients with erosive arthritis, disease duration of more than 5 years, RF and/or ACCP positivity, moderate activity, functional class 2–3. Based on the available instrumental data, systemic OP was diagnosed in 33% of patients, while DXA-densitometry was performed only in 5% of patients with osteoporotic fractures. Among the traditional RF, the most significant were female sex, age higher than 50 years, BMI less than 20 kg/m2 . The frequency of registration of these RF was significantly higher in the subgroup of patients with confirmed OP. Of the disease-associated RF, the most common were the following: duration of RA more than 5 years, activity of 2–3 degrees, high titer of RF and ACCP, X-ray stage II and higher, long term systemic GC use.Conclusions. In real practice, the diagnosis of OP in primary care in patients with RA is based on the available instrumental methods, preferably on standard radiography of bones and joints, which leads to underestimation and/or late diagnosis of OP. Patients with RA have a wide range of traditional and specific OP RFs, the assessment of which is important for determining the risk of fractures and timely prevention of OP complications.

Correction of rheumatoid swan-neck deformity of the finger using the modified Thompson-Littler method.

To investigate the outcomes of the modified Thompson-Littler (m-TL) method, a corrective surgical method utilising a dynamic tenodesis, in patients with rheumatoid swan-neck deformity. Twenty-seven fingers in 10 patients with rheumatoid arthritis (RA) underwent surgical correction. The mean age at the time of surgery was 60.3 (45-77) years, the mean duration of RA was 19.3 (4-34) years, and the mean postoperative follow-up period was 2.4 (0.5-6) years. The deformity was corrected and the proximal interphalangeal (PIP) joint pain disappeared in all operated fingers. The mean pinch power between the thumb and the operated finger increased. The active extension decreased, the active flexion increased, and the total arc of motion decreased. Comparing the range of motion by Nalebuff's type classification, the postoperative arc of motion decreased as the type advanced. The m-TL method provided a favourable outcome in cases of Type ≤III rheumatoid swan-neck deformity without severe joint deterioration at the PIP joint. Aesthetic and functional improvements were observed and the patients were satisfied with the operation.

P–450 Effects of rheumatoid arthritis and methotrexate therapy on ovarian reserve in infertile women

Abstract Study question Do patients with infertility and rheumatoid arthritis (RA) treated with methotrexate (MTX) have ovarian reserve alterations? Summary answer Women with infertility and RA treated with MTX were found to have statistically significant decrease of ovarian reserve. What is known already Rheumatoid arthritis (RA) is one of the most prominent inflammatory diseases affecting women of child-bearing age [Brouwer J. et al, 2014]. RA and its treatment may interfere with the female reproductive physiology. The vast majority of patients with RA are treated with methotrexate (MTX) which is a folate antagonist that inhibits DNA synthesis. MTX, which is the anchor drug in RA, targets actively proliferating cells including the oocytes and granulosa cells which may impair the ovarian reserve [Min Tun Kyaw et al, 2020]. Study design, size, duration A prospective case-control study that enrolled 72 female patients with infertility was conducted in the 2-year time period of September 2018 to October 2020. Participants/materials, setting, methods The main group comprised 32 patients with infertility and RA; the control group consisted of 40 women with infertility only. Patients with RA were stratified into subgroups based on whether or not they received MTX. To investigate ovarian reserve measurement of serum anti-Müllerian hormone (AMH) was used. The level of AMH was evaluated concerning RA duration and activity, as well as the age at initiation of MTX therapy, dosage, and treatment duration. Main results and the role of chance The mean age of the study population was 36±3 years. The duration of RA was 4 [3; 11] years. The low disease activity based on DAS28-ESR (disease activity score based on 28 joints using the erythrocyte sedimentation rate) prevailed(56.2%). In the main group 19(59.4%) women received MTX therapy. The MTX dosage was 15 [15;20]mg /wk, the duration of MTX therapy by the day of inclusion in the study was 18.7[1; 15]months. The AMH level was significantly lower in the main group (2.1 n /ml vs 2.73ng /ml, p = 0.043). The number of patients with decreased ovarian reserve (AMH level<1.0ng/ml) significantly prevailed in the group of patients with RA (25% vs 5%, p = 0.015). When assessing the AMH level in patients with RA who received MTX (n = 19) and patients in the control group, there was a tendency towards a decrease in the indicator in the first subgroup, but no statistically difference was found (p = 0.074). Correlation analysis of the dependence of AMH level on the patient age showed the most significant decrease in AMH in the patients with RA receiving MTX compared to the patients with RA who did not, and compared to all patients with RA regardless of the therapy received (rs=–0.563)(p < 0.05). Limitations, reasons for caution The lack of statistically significant data in certain cases may be due to the small sample size. Wider implications of the findings: RA and MTX administration are associated with a significant decrease in AMH levels. The age of initiation of the therapy is negatively correlated with the AMH level. In this regard, patients with already compromised reproductive function who are planning to receive MTX should be advised to preserve the genetic material. Trial registration number 567890

P-450 Effects of rheumatoid arthritis and methotrexate therapy on ovarian reserve in infertile women

Abstract Study question Do patients with infertility and rheumatoid arthritis (RA) treated with methotrexate (MTX) have ovarian reserve alterations? Summary answer Women with infertility and RA treated with MTX were found to have statistically significant decrease of ovarian reserve. What is known already Rheumatoid arthritis (RA) is one of the most prominent inflammatory diseases affecting women of child-bearing age [Brouwer J. et al, 2014]. RA and its treatment may interfere with the female reproductive physiology. The vast majority of patients with RA are treated with methotrexate (MTX) which is a folate antagonist that inhibits DNA synthesis. MTX, which is the anchor drug in RA, targets actively proliferating cells including the oocytes and granulosa cells which may impair the ovarian reserve [Min Tun Kyaw et al, 2020]. Study design, size, duration A prospective case-control study that enrolled 72 female patients with infertility was conducted in the 2-year time period of September 2018 to October 2020. Participants/materials, setting, methods The main group comprised 32 patients with infertility and RA; the control group consisted of 40 women with infertility only. Patients with RA were stratified into subgroups based on whether or not they received MTX. To investigate ovarian reserve measurement of serum anti-Müllerian hormone (AMH) was used. The level of AMH was evaluated concerning RA duration and activity, as well as the age at initiation of MTX therapy, dosage, and treatment duration. Main results and the role of chance The mean age of the study population was 36±3 years. The duration of RA was 4 [3;11] years. The low disease activity based on DAS28-ESR (disease activity score based on 28 joints using the erythrocyte sedimentation rate) prevailed(56.2%). In the main group 19(59.4%) women received MTX therapy. The MTX dosage was 15 [15;20]mg /wk, the duration of MTX therapy by the day of inclusion in the study was 18.7[1;15]months. The AMH level was significantly lower in the main group (2.1 n /ml vs 2.73ng /ml, p = 0.043). The number of patients with decreased ovarian reserve (AMH level<1.0ng/ml) significantly prevailed in the group of patients with RA (25% vs 5%, p = 0.015). When assessing the AMH level in patients with RA who received MTX (n = 19) and patients in the control group, there was a tendency towards a decrease in the indicator in the first subgroup, but no statistically difference was found (p = 0.074). Correlation analysis of the dependence of AMH level on the patient age showed the most significant decrease in AMH in the patients with RA receiving MTX compared to the patients with RA who did not, and compared to all patients with RA regardless of the therapy received (rs=-0.563)(p < 0.05). Limitations, reasons for caution The lack of statistically significant data in certain cases may be due to the small sample size. Wider implications of the findings RA and MTX administration are associated with a significant decrease in AMH levels. The age of initiation of the therapy is negatively correlated with the AMH level. In this regard, patients with already compromised reproductive function who are planning to receive MTX should be advised to preserve the genetic material. Trial registration number 567890

Prevalence and Factors Associated with Concomitant Chinese Medicine Use by Rheumatoid Arthritis Patients in A Multi-Ethnic Asian Population

To determine the prevalence, factors associated with and patterns of concomitant Chinese medicine (CM) with Western treatment use among patients with rheumatoid arthritis (RA) in a tertiary referral centre (Singapore General Hospital) in Singapore. We conducted a cross-sectional interviewer-administered survey of a consecutive sample of patients with RA in Singapore General Hospital centre regarding their CM use including data on patient demographics, disease characteristics, concomitant use of CM and reasons, concerns and disclosure patterns from March to August 2015. Univariate and multivariate logistic regression analyses were performed to determine the associations of CM use. Prevalence of CM use among the 258 patients surveyed (male: female 42: 216; Chinese: Malay: Indian 191: 29: 34; mean age: 61 years; mean duration of RA: 10 years) was 46.1% (119/258). On multivariate analysis, Chinese ethnicity (OR, 95% CI: 4.11, 1.49-11.36), Chinese speakers (OR, 95% CI: 2.35, 1.03-5.54), middle-income group (OR, 95% CI: 2.53, 1.01-6.31) and greater learned helplessness (OR, 95% CI: 1.13, 1.04-1.22) were significantly associated with CM use. More CM users disclosed their CM use to CM physicians (87.3%, 96/110), sought advice from them on treatment interactions (59.4%, 57/96) and how best to combine treatments (49.0%, 47/96) than did so with rheumatologists (42.0%, 50/119; 40.0%, 20/50; and 42.0%, 21/50, respectively). Forty-two percentage (29/69) of patients who concealed CM use from rheumatologists because their rheumatologists did not specifically enquire about CM use. Concomitant CM use among patients with RA treated in a tertiary referral centre in Singapore is high but voluntary disclosure is low. The associations identified can help doctors identify and enquire about CM use, minimizing potential adverse interactions.

Fibromyalgianess and glucocorticoid persistence among patients with rheumatoid arthritis.

Over one-third of patients with RA exhibit evidence of fibromyalgianess, which is associated with higher rates of disability and inadequate responsiveness to RA treatment. Patients with RA often remain on glucocorticoids long-term, despite the known risk of dose-dependent morbidity. We undertook this study to examine the relationship between fibromyalgianess and glucocorticoid persistence among RA patients. We followed participants with active RA on oral prednisone for ∼3 months after initiating a new DMARD. Fibromyalgianess was measured using the Fibromyalgia Survey Questionnaire (FSQ), previously shown to correlate with key FM features often superimposed upon RA. Severity of fibromyalgianess was stratified as follows: FSQ <8 low, FSQ 8-10 moderate and FSQ >10 high/very high. The association between baseline fibromyalgianess and glucocorticoid persistence, defined as prednisone use at 3-month follow-up visit after DMARD initiation, was assessed using multiple logistic regression adjusted for baseline demographics, RA duration, serostatus and inflammatory activity assessed using swollen joint count and CRP. Of the 97 participants on prednisone at baseline, 65% were still taking prednisone at follow-up. Fifty-seven percent of participants with low baseline fibromyalgianess had persistent glucocorticoid use, compared with 84% of participants with high or very high fibromyalgianess. After adjustment for non-inflammatory factors and inflammatory activity, participants with high/very high baseline fibromyalgianess were more likely to be taking prednisone at follow-up relative to those with low fibromyalgianess [odds ratio 4.99 (95% CI 1.20, 20.73)]. High fibromyalgianess is associated with persistent glucocorticoid use, independent of inflammatory activity.

Patterns of Anti-Inflammatory and Immunomodulating Drug Usage and Microvascular Endothelial Function in Rheumatoid Arthritis

Objectives: Specific anti-inflammatory and/or immunomodulating drugs (AIDs) can influence endothelial function which is often impaired in patients with rheumatoid arthritis (RA). We sought to determine whether overall patterns of AID usage are similarly associated with endothelial function.Methods: The reactive hyperaemia index (RHI), a marker of microvascular endothelial function, was measured in 868 RA patients reporting their intake of seven AIDs known to affect endothelial function. Latent class analysis (LCA) was performed to characterise patterns of AID usage. Models for 2–6 classes were compared using the AIC and BIC statistics and Lo-Mendell-Rubin likelihood ratio tests. Associations between the classes and RHI were adjusted for age, gender, body mass index, diabetes, HDL-cholesterol, LDL-cholesterol, family history of ischaemic heart disease, smoking status, RA duration, DAS28 score, steroid dose, existing hypertension, and C-reactive protein.Results: LCA identified five distinct AID usage classes: Class 1, generally low medication usage; Class 2, using either sulfasalazine or non-tumour necrosis factor (TNF) inhibitors; Class 3, methotrexate users; Class 4, TNF-inhibitor users; and Class 5, hydroxychloroquine users. The geometric mean for the RHI for subjects in classes 1 to 5 was 1.92, 1.81, 1.94, 2.10, and 2.07, respectively, with subjects in classes 4 and 5 having better endothelial function than subjects in class 2 (p = 0.003 for each). The glucocorticoid dosage did not influence the classes formed or the association between the classes and the RHI in sensitivity analyses.Conclusion: There were five broad patterns (classes) of AID usage in RA patients. The RHI was relatively lower in users of either sulfasalazine or non-TNF inhibitors. TNF inhibitors or hydroxychloroquine may counteract the negative effects of RA on endothelial function.

Short-term dose and duration-dependent glucocorticoid risk for cardiovascular events in glucocorticoid-naive patients with rheumatoid arthritis

ObjectivesRheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiovascular disease. Cardiovascular safety of glucocorticoids in RA is controversial and may be related to dose and duration of use....

Anti-peptidylarginine deiminase-4 antibodies at mucosal sites can activate peptidylarginine deiminase-4 enzyme activity in rheumatoid arthritis

BackgroundMucosal sites are hypothesized to play a role in the development of rheumatoid arthritis (RA). Since serum anti-peptidylarginine deiminase (PAD)4 antibodies, including a subset that cross-react with PAD3 (PAD3/4), are specific for RA and associate with severe disease, we sought to examine whether anti-PAD4 and anti-PAD3/4 antibodies were present in the lung and oral mucosa of subjects with RA and “at-risk” for RA.MethodsWe included 37 RA, 25 healthy control, and 46 subjects “at-risk” for RA based on familial RA and/or serum anti-citrullinated protein antibody (ACPA) positivity. Paired serum, sputum, and saliva were evaluated for anti-PAD4 and anti-PAD3/4 using immunoprecipitation and ACPA using ELISA. Immunoglobulins (Ig) were purified from representative samples, and their effect on citrullination of histone H3 by recombinant human PAD4 was measured by anti-citH3 immunoblot.ResultsAnti-PAD4 antibodies were detected in the serum of 6/37 (16.2%), sputum of 3/37 (8.1%), and saliva of 3/33 (9.1%) RA subjects and in the serum and sputum of 1/46 (2.2%) at-risk subjects. None of the healthy controls had anti-PAD4 antibodies at any site. Serum, sputum, and salivary anti-PAD4 antibodies were more prevalent in RA subjects with RA duration >2 years. Purified antibodies from representative anti-PAD4-positive and anti-PAD3/4-positive sputum were primarily of the IgA isotype and able to increase PAD4 enzymatic activity.ConclusionsAnti-PAD4 antibodies are present in the sputum and saliva of a portion of RA patients and are infrequent in at-risk subjects. Importantly, the ability of anti-PAD4, and particularly anti-PAD3/4, antibodies in the sputum to enhance PAD4 enzymatic activity suggests that anti-PAD4 may play an active role in the RA lung.

AB0164 THE EFFECT OF RHEUMATOID ARTHRITIS ON FEMALE FERTILITY

Background:Infertility is a disease of the reproductive system defined by the failure to achieve clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. Although rheumatoid arthritis (RA) tends to have a late onset, the disease also occurs during child-bearing years and may interfere with procreation.Objectives:The aim of this study was to compare fertility rates in women with RA with birth-year-matched references from the general population.Methods:This is a case-control study. Menopausal married women who were diagnosed in the department of Rheumatology at Hedi Chaker Hospital before the age of forty were recruited into this study as cases and apparently healthy age matched married women were recruited as controls. Demographic, clinical, immunological, radiological and therapeutic data were collected from each case using the medical record of patient. Data obtained included age, age of RA onset, duration of RA, extra-articular manifestations, Rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (ACPA), the presence of erosions on radiographs of hands and feet and the therapy.Rheumatoid arthritis and controls women were asked to state their menstrual regularity, age at menarche, age at menopause, gestity, parity, number of living children, time to first pregnancy, presence of primary or secondary infertility, the interpregnancy interval, presence of miscarriage or in utero foetal death (IUFD) or preterm delivery and their number.Results:The mean ages of the cases and controls was 54 ± 8,11 years [39, 69]. The median duration since onset of RA in the patients was 22,5 ± 10,53 years [1, 47]. The mean age of onset of the disease was 31,4 ± 6,3 [18, 39] years. Forty-nine percent (49%) of patient had extra-articular manifestations: ocular sicca syndrome in 43,8% of cases, pulmonary fibrosis in 5,3% of cases and rheumatoid nodules in 1,8 % of cases. Rheumatoid factor (RF) was present in 61,4% of cases while anti-CCP anti-body was present in 59,6% of cases.Erosive polyarthritis was found in 80,7% of patients. The mean rate of RF was 319,7 ± 462,4 UI/ml and the mean rate of anti-CCP was 185,8 ± 264.Women with RA had a statistically significant mean time to pregnancy longer than the control group. Primary infertility was seen in 15 (26,3%) patients and 2 (3,5%) controls, whereas secondary infertility was seen in 31 (54,5%) patients and 2 (3,5 %) controls. The patients were significantly more likely to have primary and secondary infertility. There were no significant differences in the age at menarche, the number of children, the gestity and the parity between the two groups. The age at menopause was statistically significant lower in the group patients than controls.Conclusion:Our study showed that RA women are more likely to have reduced fertility than general population. Although this study cannot definitively address the issue of impaired fertility among women with RA, the results are suggestive enough to warrant further research into the link between RA and fertility that takes women’s childbearing choices into account.

POS0594 MEANINGFUL IMPROVEMENT AND WORSENING IN PATIENTS WHO DO NOT ACHIEVE LDA AND SWITCH THERAPY TO A NEW BIOLOGIC OR TARGETED THERAPY: RESULTS FROM THE CORRONA REGISTRY

POS0594 MEANINGFUL IMPROVEMENT AND WORSENING IN PATIENTS WHO DO NOT ACHIEVE LDA AND SWITCH THERAPY TO A NEW BIOLOGIC OR TARGETED THERAPY: RESULTS FROM THE CORRONA REGISTRY

OP0099 EPIDEMIOLOGY AND MORTALITY OF RA-ASSOCIATED INTERSTITIAL LUNG DISEASE: DATA FROM A FRENCH ADMINISTRATIVE HEALTHCARE DATABASE

Background:Interstitial lung disease (ILD) is a common extra-articular manifestation of RA and is associated with increased morbidity and mortality.1-3 Studies have shown variability in the prevalence and mortality rate of patients with RA-associated ILD (RA-ILD).4 Further studies are needed to better characterise the epidemiology of RA-ILD.Objectives:To estimate the prevalence and incidence of clinical RA-ILD in France and to compare mortality rates between patients with RA-ILD and patients with RA without clinical ILD (RA-noILD).Methods:A historical cohort study was conducted using data from the French national claims database (SNDS) between 1 January 2013 and 31 December 2018. Adults with an RA diagnosis (International Classification of Diseases, Tenth revision [ICD-10] codes M05, M06.0, M06.8 and M06.9) and ≥2 distinct dates of DMARD delivery were included. Onset of RA was defined as the first date of occurrence between RA codes and the first known DMARD reimbursement. ILD diagnosis was defined as having ICD-10 code J84 and ≥1 computed tomography scan after, but within 1 year of, the first date of ILD occurrence. All patients had ≥6 months’ reimbursement after RA-ILD onset. The prevalence and incidence (2014–2018) of RA-ILD were estimated. The mortality rate was calculated, comparing patients with RA-ILD and patients with RA-noILD, matched 1:1 for age, sex, age at RA-ILD onset, duration of RA and presence of diabetes, arterial disease, dyslipidaemia and cardiac disease. Mortality was compared between patients with RA with and without clinical ILD in the matched population using Cox proportional hazards regression.Results:The prevalence of RA-ILD was 6.52 per 100,000 inhabitants (incidence=1.04 per 100,000 person-years). Of the 173,138 patients with RA included in the overall population, 4330 (2.5%) had clinical ILD. Patients with RA-ILD were older at RA diagnosis (mean [SD] age: 63.3 [13.7] vs 56.9 [15.2] years) and were more likely to be male (39.8% vs 27.0%) compared with patients with RA-noILD. Patients with RA-ILD were more likely to have cardiac disease (84.9% vs 63.1%), arterial disease (38.0% vs 19.3%), diabetes (21.4% vs 12.5%) and dyslipidaemia (44.7% vs 32.9%) compared with those with RA-noILD. The mortality rate in patients with clinical RA-ILD was 1.71 per 100,000 inhabitants. The mortality rate increased according to age (0.28 per 100,000 inhabitants for patients aged &lt;65 years, 4.60 per 100,000 inhabitants for patients aged 65–74 years and 11.4 per 100,000 inhabitants for patients aged ≥75 years). After matching, the adjusted mortality risk was three times higher (HR [95% CI]: 3.1 [3.1, 3.9]) in patients with RA-ILD than in those with RA-noILD (Figure 1).Conclusion:This is the largest epidemiological study of RA-ILD in France. The prevalence of clinical RA-ILD in this population was towards the lower end of previous estimates (1–58%),3 possibly due to under-reporting of claims data. However, the occurrence of clinical ILD was associated with a strong increase in mortality compared with patients with RA-noILD.

POS0095 DEVELOPPING A SCORE TO PREDICT PRECLINICAL INTERSTITIAL LUNG DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS – A CROSS-SECTIONAL STUDY FROM THE ESPOIR COHORT

Background:Interstitial lung disease (ILD) is an extra-articular manifestation of rheumatoid arthritis (RA) detected in 20% to 60% of patients with RA on high-resolution computed-tomography (HRCT) chest scan and is clinically significant in near 10%. Despite a high morbi-mortality rate, a definite strategy for preclinical ILD screening in patients with RA remains to be determined. To date, several factors have been reported to increase the risk of RA-ILD occurrence (i.e. older age at RA onset, ACPA positivity, male sex, RA disease activity, the MUC5B rs35705950 promoter variant...). However, none of these risk factors has been validated in a prospective cohort of patients with RA. The ESPOIR prospective cohort includes patients aged 18 to 70 years with recent arthritis (less than 6 months) and a definite or probable diagnosis of RA.Objectives:To identify in the ESPOIR cohort factors associated with ILD after at least 10 years of RA duration in order to develop a predictive score to identify patients with preclinical RA-ILD.Methods:An ILD detection by chest HRCT scan was systematically offered to every patient with definite RA after at least 10 years-follow-up. Chest HRCT scans were centrally reviewed by an experienced radiologist. Potential predictors of ILD were prospectively collected from baseline to the date of the HRCT scan, and all included patients were genotyped for MUC5B rs35705950. To take into account repeated measures, trajectories were determined for disease activity, C reactive protein, smoking, treatment exposure (i.e. prednisone, methotrexate [MTX] and biological disease modifying anti-rheumatic drugs [bDMARDs]). A logistic model was used to identify independent predictors for the occurrence of ILD on HRCT scans. Confidence intervals were estimated using sampling methods. A predictive score for preclinical ILD occurrence was developed based on the identified predictors.Results:163 RA patients according to 2010 ACR/EULAR classification criteria, none of whom had pulmonary symptoms, were investigated with a chest HRCT scan (128 women (78.5%), mean RA duration 13.7 ± 1.1 years, age at inclusion 47.6 y/o ± 10.4, mean disease activity score [DAS]-28 during follow up was 3.1 ± 1.0). ILD was detected in 31 patients (19.0%). The MUC5B rs35705950 minor allele frequency (MAF) was 22.2% and 10.0% in the RA-ILD and RA-noILD populations, respectively (OR univariate=2.6 CI95% [1.2-5.5], P=0.01). After logistic regression, independent predictors for preclinical RA-ILD were male sex (OR=3.9 CI95% [1.4-11.4]), older age at RA onset (OR=1.1 per year CI95% [1.0-1.2]), mean DAS-28 score during the follow-up (OR=2.0 CI95% [1.2-3.4]) and MUC5B rs35705950 T risk allele (OR=3.7 CI95% [1.4-10.4]) (Figure 1). No influence of the use of RA-related drugs (prednisone, MTX or bDMARDs) was identified as risk factor. The logistic model could predict preclinical ILD occurrence after 13 years of RA duration with an AUC=0.82 CI95% (0.72-0.91). A predictive score for preclinical RA-ILD based on the 4 identified predictive risk factors was developed (Sensitivity 80%, Specificity 56%).Figure 1.Factors independently associated with preclinical ILD after 13 years of RA durationConclusion:In this cross-sectional study of the prospective ESPOIR cohort, we identified clinical and genetic predictors for ILD after 13 years of RA duration. We developed a predictive score that could improve risk stratification for preclinical RA-ILD and help physicians identify patients with RA in whom a HRCT scan should be performed.Disclosure of Interests:Pierre-Antoine Juge Consultant of: BMS, Benjamin Granger: None declared, Marie-Pierre Debray: None declared, Esther Ebstein: None declared, Fabienne Louis Sidney: None declared, Joanna KEDRA: None declared, Raphael Borie: None declared, Arnaud Constantin Consultant of: Bristol-Meyers Squibb, Chugai, Roche, Abbvie, MSD, Pfizer, and UCB, Bernard Combe Consultant of: Abbvie, Bristol-Meyers Squibb, Lilly, MSD, Janssen, Pfizer, Roche, Chigai, and Sanofi, Grant/research support from: Abbvie, Bristol-Meyers Squibb, Lilly, MSD, Janssen, Pfizer, Roche, Chugai, and Sanofi, René-Marc Flipo Consultant of: Bristol-Meyers Squibb, Roche, Chugai, Abbvie, and Pfizer, Grant/research support from: Roche, Chugai, Abbvie, and Pfizer, Xavier Mariette Consultant of: Bristol-Meyers Squibb, GSK, Janssen, Pfizer, and UCB, Olivier VITTECOQ Consultant of: Bristol Myers Squibb, Roche, Chugai, MSD, Novartis, Pfizer, Abbvie, and Lilly, Alain Saraux Consultant of: Roche, Chugai, and Bristol-Meyers Squibb, Grant/research support from: Roche, Chugai, and Bristol-Meyers Squibb, Guillermo CARVAJAL ALEGRIA: None declared, Jean Sibilia Consultant of: Roche, Chugai, Bristol-Meyers Squibb, UCB, GSK, LFB, Actelion, Pfizer, MSD, Novartis, Amgen, Hospira, AbbVie, Sandoz, Gilead, Lilly, Sanofi, Janssen, and Mylan, Francis Berenbaum Consultant of: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Elli Lilly, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma, Caroline Kannengiesser: None declared, Catherine Boileau: None declared, Bruno Crestani Consultant of: Boehringer Ingelheim, Roche, Sanofi, Apellis, Astra-Zeneca, Grant/research support from: MedImmune, Boehringer Ingelheim, Bruno Fautrel Consultant of: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, SOBI, UCB, Grant/research support from: AbbVie, MSD, Pfizer, Philippe Dieudé: None declared

OP0122 COMPARATIVE EFFECTIVENESS OF JAKI VERSUS BDMARDS; A NATIONWIDE STUDY IN RA

Background:The Janus kinase inhibitors (JAKi) have been increasingly used for the treatment of rheumatoid arthritis (RA) in Sweden, with baricitinib representing ~80% of prescriptions. Evidence regarding the comparative effectiveness of JAKis versus biologics (bDMARDs), and in particular non- tumour-necrosis-factor inhibitor (TNFi) bDMARDs, in real-life is limited.Objectives:To compare RA patients treated with bDMARDs and JAKi in Sweden, in terms of: (1) patient characteristics at treatment start; (2) proportions of patients remaining on therapy, and response rates, at 12 months.Methods:RA patients starting treatment in 2017 and 2018 with either a TNFi, rituximab, abatacept, interleukin 6 inhibitors (IL6i) or a JAKi as different lines of treatment were identified in the Swedish Rheumatology Quality Register. One patient could contribute with more than one treatment episode.Treatment response at 12 months was measured as EULAR good response, HAQ improvement &gt;0.2 units, DAS28 and CDAI remission, and as 0 tender and swollen joint counts (28JC). Patients were classified as non-responders if they stopped treatment before evaluation due to safety or inefficacy. Responses for patients who stopped treatment due to pregnancy or death and patients on treatment but with missing response were imputed using multiple imputation.Proportions of responders and differences in proportions between treatment groups, adjusted using inverse probability of treatment weighting, were estimated using linear regression with robust standard errors.Results:JAKi were often used after bDMARDs, and less frequently prescribed in combination with methotrexate. Measured comorbidities were less frequent among JAKi initiators than among non-TNFi biologic initiators, but RA activity was similar (Table).Table 1.Patient characteristics at treatment initiationCharacteristicMedian (IQR) or N (%)AbataceptIL6iRituximabTNFiJAKiTreatment Starts6945346923497905Age63 (53-71)59 (48-70)65 (54-73)59 (47-68)60 (51-70)Female543 (78)441 (83)519 (75)2739 (78)759 (84)RA duration (years)13 (5-21)10 (5-18)12 (6-22)9 (3-17)13 (7-22)Rheum. factor535 (79)385 (73)588 (87)2405 (70)686 (77)DAS284.8 (3.9-5.6)4.9 (4.0-5.7)4.7 (3.8-5.5)4.4 (3.4-5.3)4.7 (3.9-5.7)HAQ1.3 (0.8-1.6)1.3 (0.8-1.8)1.3 (0.8-1.8)1.0 (0.5-1.4)1.3 (0.8-1.8)Tender joints5 (2-9)6 (3-10)5 (2-9)4 (2-8)6 (2-10)Swollen joints4 (2-6)4 (2-7)4 (2-7)3 (1-6)4 (2-7)ts/bDMARD line3 (2-4)3 (2-4)2 (1-4)1 (1-2)4 (2-6)At least one prev. TNFi539 (78)442 (83)457 (66)1448 (41)770 (85)At least one prev. non-TNFi271 (39)220 (41)243 (35)441 (13)584 (65)Methotrexate co-treatment264 (50)172 (40)286 (53)1708 (62)296 (40)Glucocorticoids co-treatment247 (47)186 (43)275 (51)1126 (41)389 (53)Cancer*90 (2.8)64 (2.3)363 (7.7)410 (1.8)20 (2.2)Cardio-vascular dis.*245 (7.5)123 (4.4)322 (6.8)749 (3.4)41 (4.4)Chronic respiratory dis.*303 (9.3)140 (5.0)473 (10.0)721 (3.2)50 (5.4)Diabetes*324 (9.9)216 (7.7)456 (9.7)1479 (6.7)69 (7.5)* any diagnosis within 5 years before start Adjusted differences in proportion with each response outcomeIn a crude comparison, 65% (61%-68%) of JAKi, 62% (59%-66%) of abatacept, 58% (53%-62%) of IL6i, 80% (77%-83%) of rituximab and 68% (67%-70%) of TNFi initiators remained on treatment at 12 months after start. Also, JAKi showed lower overall responder proportions than TNFi, rituximab and IL6i.After adjustment for demographic and socio-economic factors, RA disease activity, previous use of ts/bDMARDs, co-medication with glucocorticoids and methotrexate and comorbidities at baseline, no significant differences in responder proportions between JAKi and bDMARDs remained (Figure). Furthermore, the adjusted proportions of patients on treatment were higher for JAKi and rituximab than for the other bDMARDs.Conclusion:This preliminary analysis of patients treated in clinical practice found no statistically significant difference in effectiveness between JAKi and bDMARDs.Disclosure of Interests:Andrei Barbulescu: None declared, Johan Askling Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB. These entities have entered into agreements with Karolinska Institutet with JA as principal investigator, mainly in the context of safety monitoring of biologics via the ARTIS national safety monitoring system, Katerina Chatzidionysiou Speakers bureau: Eli Lilly, Abbvie and Pfizer, Consultant of: Eli Lilly, Abbvie and Pfizer, Helena Forsblad-d’Elia: None declared, Alf Kastbom Employee of: Sanofi, Ulf Lindström: None declared, Carl Turesson Speakers bureau: Abbvie, Bristol-Myers Squibb, Medac, Pfizer, Roche, Consultant of: Roche, Grant/research support from: Bristol-Myers Squibb, Thomas Frisell: None declared

POS0575 THE PATIENT GLOBAL ASSESSMENT (PGA) OF DISEASE ACTIVITY COLLECTS DIFFERENT INFORMATION IN EARLY COMPARED TO ESTABLISHED RHEUMATOID ARTHRITIS

Background:The patient global assessment (PGA) is the most widely used patient-reported measure in rheumatoid arthritis (RA), being a component of disease activity scores and definitions of remission. Studies have however shown that, at least in established RA, PGA is mostly associated with pain, functional limitation, psychological distress and comorbidities, rather than with objective measures of inflammation. As such, the inclusion of PGA as a driver of intensification of immunosuppressive therapy is been questioned. Determinants of PGA may however differ in the earliest stages of RA, when pain processing mechanisms and damage accrual have not occurred yet. Whether the association of PGA with disease activity in RA changes over time is at present undetermined.Objectives:To analyze the associations between PGA and disease activity measures in patients with RA across different phases of the disease.Methods:1.002 RA patients from two independent cohorts were included: 1) a prospective longitudinal cohort of early RA (&lt;12 months of symptoms) (n=601) with an observation period of 24 months upon initiation of therapy with methotrexate; 2) a cross-sectional cohort of established RA (duration &gt;5 years) (n=401) with inadequate response to methotrexate. Determinants of PGA were assessed by Pearson’s correlation coefficients and multivariable linear regression.Results:In early RA, median (IQR) symptom duration at inclusion was 15 (9-27) weeks, 71.5% of the patients were female, 49.3% were autoantibody-positive, and 30% had radiographic evidence of ≥1 erosion. The mean (SD) DAS28 was 4.94 (1.19), and the mean (SD) PGA 57.6 (26.6). The proportion of patients at least in low disease activity (DAS28 &lt;3.2) after 6, 12 and 24 months of treatment was 49.9%, 57.4% and 67% respectively. The associations of PGA with pain and functional limitation were moderate to good (r &gt;0.40) at all time points, and were independent of other co-variates (Table 1). Swollen joints (SJC28) were independently and directly associated with PGA at all time points until 12 months, whilst the association become indirect at 24 months (Table 1). In ACPA-positive patients, PGA at 6 and 12 months was weakly but still significantly associated with SJC28 even in low disease activity states (adj r 0.15 and 0.13, p&lt;0.05). Patients with established RA had a mean [SD] DAS28 of 5.3 [1.2] and were ACPA-positive in 69.6% of the cases. Independent determinants of PGA were pain, HAQ and tender joints, whilst no associations with SJC28 and acute phase reactants were found neither in the overall cohort nor in ACPA-positive patients.Conclusion:In established RA, PGA appears mostly related to factors outside the core domains of disease activity. In contrast, in the early phases of the disease, PGA may more strictly collect information on inflammatory-related symptoms. Better understanding of the relationship between patient reported outcomes and disease activity in the various phases of RA may thus be needed before introducing definitive changes in the current definitions of disease activity.

POS0666 TREATMENT EFFECTIVENESS OF UPADACITINIB AT 3 MONTHS IN US PATIENTS WITH RHEUMATOID ARTHRITIS FROM THE UNITED RHEUMATOLOGY NORMALIZED INTEGRATED COMMUNITY EVIDENCE (NICE[TM]) REAL-WORLD DATA

Background:Upadacitinib (UPA), an oral Janus kinase inhibitor (JAKi), has demonstrated efficacy in the phase 3 SELECT clinical program, conducted across a range of patients (pts) with rheumatoid arthritis (RA).1–6 Real-world data for UPA, including in pts previously treated with a JAKi, have not yet been reported since global approvals beginning in 2019.Objectives:To assess the characteristics of US-based pts receiving UPA and its effectiveness in clinical practice at 3 months.Methods:This observational study included US-based pts from the United Rheumatology Normalized Integrated Community Evidence (UR-NICE) database who initiated UPA 15 mg once daily from FDA approval (August 2019) to July 31, 2020 and had ≥6-month pre-baseline data available. Effectiveness was assessed in pts with a reported Clinical Disease Activity Index (CDAI) score at 3 months after UPA initiation and included proportions of pts achieving CDAI remission (≤2.8), CDAI low disease activity (≤10), other disease activity measures, and pt-reported outcomes. A subgroup analysis assessed UPA effectiveness in pts with or without prior tofacitinib (TOFA) treatment.Results:This analysis included 252 pts treated with UPA 15 mg, of whom 98 (38.9%) received UPA monotherapy and 154 (61.1%) received UPA combined with conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs). 64.3% of pts were from the Southern region of the USA. 86.1%, 72.2%, and 47.6% of pts had been previously treated with csDMARDs, biologic DMARDs, and JAKis, respectively. Baseline characteristics were largely similar between UPA monotherapy and combination therapy groups and those with or without prior TOFA treatment (Table 1). Pts with prior TOFA treatment had a longer duration of RA since diagnosis and higher steroid use versus those without. UPA 15 mg improved disease activity scores (including CDAI) and pt-reported outcomes (including physical function and pain) after 3 months of treatment (Figure 1). Similar effectiveness was observed with UPA 15 mg in pts with or without prior TOFA treatment.Conclusion:In the UR-NICE real-world database of US-based pts, improvements in clinical and pt-reported outcomes were observed at 3 months in UPA-treated pts with RA, including those with or without prior TOFA treatment, despite the treatment-refractory population included in this dataset.