American College Of Rheumatology/European League Against Rheumatism Research Articles

Genetic heterogeneity of pediatric systemic lupus erythematosus with lymphoproliferation.

Systemic lupus erythematosus (SLE) is a chronic, rare autoimmune disease. In recent years, multiple monogenic diseases with early onset autoimmunity and lymphoproliferation have been identified, such as autoimmune lymphoproliferative syndrome, rat sarcoma (RAS)-associated autoimmune leukoproliferative disease, signal transducer and activator of transcription 3 gain-of-function syndrome and interleukin-2 receptor α deficiency. Therefore, we performed whole-exome sequencing in children with SLE with lymphoproliferation to identify genes associated with these conditions.We enrolled 7 patients with SLE with lymphoproliferation from different families. Demographic data, clinical manifestations, laboratory and histopathologic findings, treatment, and outcome were documented. Whole-exome sequencing was performed in 7 patients and their families. Suspected variants were confirmed by Sanger sequencing. Protein levels were detected in patients with gene mutations by western blot.Four patients were male, and 3 were female. No consanguinity was reported within the 7 families. The average age at onset was 5.0 years (range: 1.2–10.0 years). The most common features were renal (7/7 patients) and hematologic (6/7 patients) involvement and recurrent fever (6/7 patients), while only 2 patients presented with skin involvement. Antinuclear antibodies at a titer of ≥1:320 were positive in all patients. All patients fulfilled four 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria for the classification of SLE. We identified a somatic activating NRAS variant (c.38 A>G, p.G13C) in peripheral venous blood from 4 patients, at levels ranging from 8.8% to 42.8% in variant tissues that were absent from their parents. B cell lymphoma (BCL)-2-interacting mediator of cell death levels in peripheral blood mononuclear cells from 4 patients were markedly reduced, whereas those in the control were normal. Another 2 mutations, c.559C>T (p.Q187X) in the TNFAIP3 gene and c.3061G>A (p.E1021K) in the PIK3CD gene were detected in 2 patients.The SLE is a novel phenotype of somatic mutations in the NRAS gene and germline mutations in the PI3CKD gene. These genes, NRAS, TNFAIP3, and PIK3CD, should be considered candidates for children with SLE with lymphoproliferation. If patients with SLE and lymphoproliferation present with renal and hematologic involvement and recurrent fever, they need gene testing, especially male patients.

Is treat-to-target really working in rheumatoid arthritis? a longitudinal analysis of a cohort of patients treated in daily practice (RA BIODAM)

ObjectivesTo investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target.MethodsRA patients from 10 countries starting/changing conventional synthetic...

Testing different thresholds for patient global assessment in defining remission for rheumatoid arthritis: are the current ACR/EULAR Boolean criteria optimal?

ObjectivesThis study aimed to evaluate different patient global assessment (PGA) cut-offs required in the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean remission definition for their utility in rheumatoid...

Application of the 2019 European League Against Rheumatism/American College of Rheumatology systemic lupus erythematosus classification criteria in clinical practice: a single center experience.

Originally developed as research tools, different classification criteria sets for systemic lupus erythematosus (SLE) are also used to diagnose SLE in routine clinical care. The recently developed European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2019 criteria set is noted to perform better than previous SLE classification criteria. This study applied the new criteria schema to a tertiary center SLE cohort, ascertained its performance, and identified the clinical characteristics of patients who did not fulfill these criteria. From the 217 patients who were included, 11 (5%) did not meet the new criteria, mainly because of the antinuclear antibody entry criterion, resulting in a diagnostic sensitivity of 94%. Within this group, we found that constitutional and renal manifestations were unusual. Additionally, specific SLE antibodies as well as hypocomplementemia were less likely to be present. We did not observe a statistically significant difference in outcomes between the two groups of patients (fulfilling vs. unfulfilling the new criteria). We conclude that the EULAR/ACR criteria may misclassify a small subset of SLE patients with milder disease. It is important to be cognizant of key clinical and serologic features of these patients and treat them accordingly to prevent further irreversible damage.

Clinical efficacy and safety of tocilizumab in the treatment of seropositive rheumatoid arthritis patients in India

Background: Tocilizumab (TCZ) is a human interleukin (IL)-6 receptor (IL-6R) antibody which competitively inhibits IL-6 signal transduction. Clinical efficacy and safety of TCZ in the treatment of rheumatoid arthritis (RA) and other autoimmune conditions have been established. However, there is a lack of data on its use in the Indian population. Objective: The objective was to study the clinical efficacy and safety of TCZ in Indian patients with seropositive RA. Patients and Methods: This was a prospective, observational single-center study conducted at a tertiary care rheumatology center. All patients were more than 16 years of age, fulfilled the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA, and had at least moderate disease activity as measured by disease activity score-28 joints erythrocyte sedimentation rate (DAS28-ESR) ≥3.2 at enrollment while on at least two disease-modifying antirheumatic drugs. Patients with latent tuberculous infection were excluded from the study. Six doses of TCZ were administered at 8 mg/kg body weight dose at four weekly interval and clinical response was assessed at each visit. Results: All 30 patients enrolled completed the study. Baseline DAS28-ESR was 5.03 (SD0.39) which improved to 2.4 (△-2.6; 95% confidence interval: 2.30–3.04; P Conclusions: TCZ is an effective and safe option for the treatment of seropositive RA.

Effect of low-dose aspirin on platelet aggregation inhibition in patients with rheumatoid arthritis

Introduction : The risk for coronary artery disease (CAD) and mortality has increased in patients with rheumatoid arthritis (RA). Aspirin has anti-thrombotic effects and causes reduction in CAD occurrence in high-risk individuals. The objective of present project was evaluating the influence of low-dose aspirin on inhibition of platelet aggregation in patients with RA. Methods: Forty-eight subjects with RA diagnosed based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria and age- and sex-matched healthy participants were studied. All subjects received 81 mg/day aspirin for 10 days. Level of the serum thromboxane B2 (sTxB2), a permanent metabolite of thromboxane A2 (TxA2), was measured before and after therapy using enzyme-linked immunosorbent assay (ELISA) kit. The impotency to decrease sTxB2 production to less than 10 ng/ml indicates suboptimal suppression of platelet aggregation via aspirin. Results: Low-dose aspirin decreased sTxB2 significantly compared with baseline in patients with RA [median interquartile range (IQR): 25.72 (11.78, 90.10) to 7.74 (5.80, 8.82), P < 0.001] and in healthy controls [median (IQR): 40.50 (33.25, 50.90) to 7.30 (4.75, 8.85), P < 0.001]. No remarkable changes were seen in sTxB2 between patients and controls after adjustment (P > 0.050). Pharmacologic influence of aspirin was suboptimal in 6.25% of cases in the presence of higher erythrocyte sedimentation rate (ESR) and in 2.7% of controls. Low-dose aspirin decreased sTxB2 significantly only in patients with Framingham Risk Score (FRS) < 10%. Conclusion: Low-dose aspirin decreased sTxB2 level and suppressed platelet aggregation and therefore, was effective in primary prevention of cardiovascular (CV) events in patients with RA; however, additional studies are required to reach accurate conclusions.

The Brazilian Society of Rheumatology recommendations on investigation and diagnosis of systemic autoimmune myopathies

BackgroundThis research is recommended by the Myopathy Committee of the Brazilian Society of Rheumatology for the investigation and diagnosis of systemic autoimmune myopathies.BodyA systematic literature review was performed in the Embase, Medline (PubMed) and Cochrane databases, including studies published until October 2018. PRISMA was used for the review, and the articles were evaluated, based on the Oxford levels of evidence. Ten recommendations were developed addressing different aspects of systemic autoimmune myopathy investigation and diagnosis.ConclusionsThe European League Against Rheumatism/ American College of Rheumatology (EULAR/ACR) classification stands out for the diagnosis of systemic autoimmune myopathies. Muscular biopsy is essential, aided by muscular magnetic resonance images and electroneuromyography in complementary research. Analysis of the factors related to prognosis with the evaluation of extramuscular manifestations, and comorbidities and intense investigation regarding differential diagnoses are mandatory.

Rheumatoid Arthritis: a debilitating battle with the human immune system

Rheumatoid arthritis (RA) is an autoimmune disease in which the immune system mistakenly attacks different regions of the body, notably joints in the hands, knees, elbows, and feet. As a result, these regions become inflamed and lead to pain, swelling, and subsequent joint damage. This can affect daily activities, mental well-being, quality of life, and may decrease expected life span. As of today, there is no cure for RA and its etiology remains elusive. RA is classified using the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Criteria and treated according to the Canadian Rheumatology Association (CRA) Guidelines, which mainly focus on pharmacological interventions. Three classes of pharmaceutical agents havebeen effective in treating RA symptoms - disease modifying antirheumatic drugs (DMARDs), including conventional synthetic and advanced therapeutics (eg biologics, JAK inhibitors), nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids. DMARDs, specifically methotrexate, hydroxychloroquine, and sulfasalazine, are usually used early to treat the underlying course of the disease. However, potential adverse drug reactions may cause some patients to discontinue or experience lack of benefit over time. Non-traditional therapy, such as diet modification, physical activity, and mindfulness-based stress reduction activities, may be adjunctive treatment for pain, fatigue, and overall mental health. Nevertheless, finding optimal treatments remains largely empirical and patient-specific. A better understanding of RA progression is needed to accurately treat the underlying disease, while improving symptoms and minimizing adverse effects. An integrated approach that incorporates both pharmacological and nonpharmacological therapies may provide more comprehensive management of RA.

Rheumatoid Arthritis Treatment. A Back to the Drawing Board Project or High Expectations for Low Unmet Needs?

Despite the significant progress in Rheumatoid Arthritis (RA) therapeutics, there are several reports in the literature claiming that the size of unmet needs in RA is large. In the era before biologics, there was indeed a significant number of patients who did not achieve low disease activity (LDA) or disease remission due to limited therapeutic choices in the doctors’ armamentarium. Treatment wise, great progress has been achieved over the last decades with the discovery and introduction in therapeutics of new molecules, such as the biological (b) disease-modifying anti-rheumatic drugs (DMARDs), and the targeted synthetic (ts) DMARDs. Today, with such a plethora of conventional synthetic (cs) DMARDs, tsDMARDs, and bDMARDs, why are we unable to successfully treat RA patients? What is wrong? However, a new drug for RA does not mean it is necessary to switch to a new treatment. It is very easy to change and switch therapies when the patient complains about pain and stiffness. In this setting, it is obligatory to rule out other comorbidities and disorders that may be the cause of the pain first. Thus, clinicians must have a deep knowledge of the drug therapy and be able to adjust the treatment when needed. A minute clinical examination must be carried out on every visit with close monitoring of the patient. A treat-to-target (T2T) approach and the application of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) recommendations and strategies should minimize the unmet needs.

Comparison of sexual function in Tunisian women with rheumatoid arthritis and healthy controls.

To evaluate sexual function in Tunisian women with rheumatoid arthritis (RA) and to compare it with that in voluntary healthy controls. We conducted a cross-sectional study including 71 women with a confirmed diagnosis of RA according to the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 Criteria and 71 healthy age-matched controls. Clinical and sociodemographic characteristics were collected. Patients and controls were asked to complete the Female Sexual Function Index (FSFI). It contains 19 questions, assessing six areas of female sexual function in the previous 4weeks. The sexual dysfunction was defined as an FSFI score less than or equal to 26.55. The patients' self-perception of their sexuality was assessed, and the frequency of sexual intercourse was noted. The prevalence of female sexual dysfunction in women with RA was 49.3% versus 23.9% in controls, with a significant difference (p = 0.002). Comparison between both groups as regards the mean of area scores of FSFI revealed that desire, arousal, and satisfaction in patients with RA were significantly lower than those in the control group (p = 0.05, p = 0.038, and p = 0.024, respectively). The score of lubrification, orgasm, and pain was comparable between the two groups. In univariate analysis, a significant association was found between sexual dysfunction and pain (p = 0.001), tender joint counts (p = 0.04), DAS28 ESR (p = 0.043), fatigue (p = 0.028), and functional disability (p = 0.02). No association was found between sexual dysfunction and treatment. In multivariate analysis, only pain was a predictive factor of sexual dysfunction in patients (p = 0.05, OR = 1.26 [1.16-1.3]). Based on patients' self-perception of their sexual function, 26.1% of patients reported a negative impact of RA on their sex life. According to them, the main factors influencing sexuality were joint pain (60.6%) and fatigue (51%). Moreover, 59% of patients reported a decrease in the frequency of sexual intercourse after the diagnosis of RA. However, no statistically significant difference was found between patients and controls in the frequency of sexual intercourse (p = 1). Our study suggests that patients with RA experience high level of impairment of sexual function in comparison with a control group. Health providers must consider sexual function as an important part of quality of life. A therapeutic education directed towards a patient could be proposed to approach sexuality.Key Points• The prevalence of female sexual dysfunction is higher in women with rheumatoid arthritis than in controls.• In multivariate analysis, the global pain intensity visual analog scale was the only predictive factor of sexual dysfunction in patients.• Based on patients' self-perception, joint pain and fatigue are the main factors influencing sexuality.

Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol

Trial designWe present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis.MethodsThe study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52 weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other’s assessments for the duration of the study.ConclusionsThere is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the “at risk” state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA.Trial registrationCurrent Controlled Trials, ID: ISRCTN46017566. Registered on 4 July 2014.

Association of 17 Definitions of Remission with Functional Status in a Large Clinical Practice Cohort of Patients with Rheumatoid Arthritis.

To compare the association between different remission criteria and physical function in patients with rheumatoid arthritis followed in clinical practice. Longitudinal data from the METEOR database were used. Seventeen definitions of remission were tested: American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean-based; Simplified/Clinical Disease Activity Index (SDAI/CDAI); and 14 Disease Activity Score (DAS)-based definitions. Health Assessment Questionnaire (HAQ) ≤ 0.5 was defined as good functional status. Associations were investigated using generalized estimating equations. Potential confounders were tested and sensitivity analyses performed. Data from 32,915 patients (157,899 visits) were available. The most stringent definition of remission was the ACR/EULAR Boolean-based definition (1.9%). The proportion of patients with HAQ ≤ 0.5 was higher for the most stringent definitions, although it never reached 100%. However, this also meant that, for the most stringent criteria, many patients in nonremission had HAQ ≤ 0.5. All remission definitions were associated with better function, with the strongest degree of association observed for the SDAI (adjusted OR 3.36, 95% CI 3.01-3.74). The 17 definitions of remission confirmed their validity against physical function in a large international clinical practice setting. Achievement of remission according to any of the indices may be more important than the use of a specific index. A multidimensional approach, targeted at wider goals than disease control, is necessary to help all patients achieve the best possible functional status.

Ultrasound as a Useful Tool in the Diagnosis of Rheumatoid Arthritis in Patients With Undifferentiated Arthritis.

Nowadays, rheumatologists face challenges in finding an effective method to classify and treat patients with undifferentiated arthritis (UA). There is a need for new tools that could ensure accurate characterization of inflammatory processes in these patients. The aim of this study was to investigate if a characterization of UA patients using ultrasound (US) may help to fulfill the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) classification criteria in a real-life cohort. We conducted a cross-sectional study in 2 rheumatology care clinics. Patients not fulfilling the 2010 ACR/EULAR RA criteria were included. On the examination day, all patients underwent a physical examination, radiography, and US. The 7-joint US score was adopted to scan all patients. The US was performed according to EULAR criteria and interpreted by Outcome Measures in Rheumatology definitions. Gray-scale and power Doppler synovitis and tenosynovitis were scored. Bone erosions were also evaluated during the US examination. A total of 204 patients were included. The diagnosis was modified from UA to RA in 86 patients (42.1%). Also, the final score of the 2010 ACR/EULAR RA classification criteria changed from a mean of 4.6 to 6.5 after the US examination. In addition to synovitis, a wide range of tenosynovitis and bone erosions were detected by US. Synovitis was more frequently detected in second metacarpophalangeal joint followed by second metatarsophalangeal joint (MTPj) and fifth MTPj. The tendons of the wrist and second and third fingers were the most affected. In relation to bone erosions, second metacarpophalangeal joint and fifth MTPj were the joints with more proportion of anatomical damage. The US demonstrated to be useful to help accurately classify as RA patients previously diagnosed with UA.

The value of the simplified RAMRIS-5 in early RA patients under methotrexate therapy using high-field MRI

BackgroundThe aim of the study was to evaluate a simplified version of the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) for five joints of the hand (RAMRIS-5) in patients with early rheumatoid arthritis (RA) before and after the initiation of methotrexate (MTX) therapy using high-resolution, 3-T magnetic resonance imaging (MRI).MethodsTwenty-eight patients with a seropositive, early RA (disease duration of less than 6 months (range 2–23 weeks)) according to 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria (mean age 56.8 years, range 39–74) were prospectively assessed with a baseline investigation including clinical assessment (disease activity score of 28 joints (DAS-28) and C-reactive protein (CRP)) and 3-T MRI of the clinically dominant hand. Follow-up visits were performed 3 and 6 months after initiation of a MTX therapy at baseline. MRI scans were analyzed in accordance with RAMRIS and the simplified RAMRIS-5.ResultsDAS-28 and CRP decreased significantly after initiation of MTX therapy. Even though erosion scores increased over time, RAMRIS and RAMRIS-5 also decreased significantly after the start of therapy. There was a strong correlation between the total RAMRIS-5 and RAMRIS at baseline (r = 0.838; P <0.001) and follow-up (3 months: r = 0.876; P <0.001; 6 months: r = 0.897; P <0.001). In the short term (3-month follow-up), RAMRIS and RAMRIS-5 demonstrated similar ability to detect changes for all subgroups (bone edema, erosion, and synovitis). In the long-term comparison (6-month follow-up), RAMRIS-5 also showed similar effectiveness when detecting changes in bone edema and erosion compared with RAMRIS. Deviations occurred regarding only synovitis, where change was slightly higher in RAMRIS-5: SRM (RAMRIS) = 0.07 ± 0.14; SRM (RAMRIS-5) = 0.34 ± 0.06.ConclusionsThree-Tesla MRI-based RAMRIS-5 is a simplified and resource-saving RAMRIS score which compares favorably with the RAMRIS when detecting changes in early RA. Even though there is a slight abbreviation between RAMRIS-5 and the original score regarding the change of synovitis, it may be used for diagnosis and therapy monitoring in follow-up evaluations.

Diagnostic Value of Lip Mucosal Impression Cytology and &lt;i&gt;in vivo&lt;/i&gt; Confocal Microscopy in Primary Sjogren's Syndrome

Background: Labial gland biopsies play a significant role in diagnosing primary Sjogren's syndrome (pSS) but their clinical use is limited because of their invasiveness. We assessed the value of impression cytology (IC) and in vivo confocal microscopy (IVCM) for diagnosing pSS. Methods: Consecutive patients with clinically suspected pSS (n = 102) were enrolled. According to the American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) criteria, all patients underwent labial gland biopsies, serum anti-Sjogren's syndrome A (SSA)/Ro antibody testing, Schirmer's tests (STs), corneal staining and unstimulated whole saliva flow (UWS) determinations. The patients were divided into pSS (n = 28) and control (n = 74) groups, all underwent lip mucosa IC and IVCM analyses. The salivary gland ultrasonography (SGUS) score, ocular surface disease index (OSDI), tear meniscus height (TMH), tear film breakup time (BUT), and meibomian gland score were recorded. The associations between IC/IVCM parameters and clinical/laboratory results were analyzed. Findings: The absolute agreements between lip mucosal IC and the ACR-EULAR criteria (98·04%)/ labial gland biopsy (97·06%) were good. A combination of IC and anti-SSA/Ro antibody determination showed high predictive value for diagnosing pSS. Compared with controls, IVCM revealed significant lip mucosal epithelium thinning and lamina propria atrophy in the pSS group (both, P < 0·001). The sensitivities for diagnosing pSS corresponding to a lamina propria thickness ≤126 μm and a gland diameter ≤90 μm were both 85·71%; the specificities were 90·54% and 100%, respectively. A combination of IVCM results and anti-SSA/Ro antibody results showed high predictive value for diagnosing pSS. Interpretation: Characteristic cellular and morphological changes of lip mucosa in patients with pSS could be detected by IC and IVCM. These noninvasive and easy-to-perform examinations may be an alternative to labial gland biopsies for diagnosing pSS. Funding Statement: This study was supported by a grant from the Beijing Health and Family Planning Commission, Capital’s Funds for Health Improvement and Research [Grant numbers: CFH2018-2-4093]. Declaration of Interests: The authors state: None of the authors have any conflicts of interest to report. Ethics Approval Statement: The study was performed according to the principles of the Declaration of Helsinki and was approved by the Human Research and Ethics Committee, Peking University Third Hospital; written informed consent was obtained from each study participant.

Cyclophosphamide in a cohort of biologic naïve rheumatoid arthritis patients resistant to conventional DMARDs

Background: Rheumatoid Arthritis (RA) poses a significant economic burden in health services worldwide. The most important factor influences poor outcome in RA patients is the lack of drug adherence that is mainly due to financial cost and poor patient education. There is a significant number of RA patients fail to respond or show poor response to conventional DMARDs and they can’t afford the high cost of biologic therapy. Cyclophosphamide (CYC) is an immunosuppressive drug that inhibit the actively dividing inflammatory cells, suppressing the inflammatory cytokines and stops inflammation induced joint erosions in RA patients. To evaluate the efficacy of IV pulse methylprednisolone (MP) and Cyclophosphamide (CYC) in induction of remission in a cohort biologic naive aggressive RA patients resistant to different combinations of conventional Disease-Modifying Anti Rheumatic Drugs (DMARDs). Methods and Findings: A prospective observational study performed on 30 RA patients diagnosed according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria, who fail to respond to different combinations of conventional DMARDs for at least two years. All patients subjected to history taking, rheumatological examination, assessment of RA disease activity, laboratory investigations; Complete Blood Count (CBC), Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Rheumatoid Factor (RF) and anti-cyclic citrullinated peptide antibody (ACCP) recorded at baseline and after 6 months (study endpoint). All RA patients have been treated with monthly IV pulse 1 g MP and CYC at a dose 500 mg/m2 surface area for 6 months. On comparing baseline to endpoint data there was a significant reduction in all disease activity parameters: number of tender and swollen joints, disease activity scores 28 (DAS28), Health Assessment Questionnaire (HAQ), Visual Analog Scale (VAS), ESR, CRP and platelet (PLT) level, with increase in haemoglobin in all treated patients at the study endpoint. No significant difference between RF, ACCP seropositivity and different disease activity markers, except for increased haemoglobin in RF positive and reduction of PLT count in positive ACCP patients’ post-treatment. High CRP at baseline indicates poor prognosis, response to pulse CYC therapy and high VAS at the study endpoint. Conclusions: Pulse MP and CYC monthly for 6 months significantly benefit in induction of remission in a biologic naive aggressive RA patients resistant to different combinations of conventional DMARDs.

Development of lymphoma in patients with primary Sjögren syndromes

Background: Lymphoma is the main complication of primary Sjogren syndrome (pSS). The aim of this study was to describe the prevalence and incidence rate of lymphoma in patients with pSS in eleven centers in Argentina. To determine the frequency of commitment of the domains of the baseline clinical ESSDAI in the patients who developed lymphoma in the course of their follow-up and compare it with the rest of the sample. Methods and findings: We included patients older than 18 years with a diagnosis of pSS according to American College of Rheumatology/European League against Rheumatism (ACR/EULAR)2002/2016 criteria, included in a multi-center Argentine database. Patients diagnosed with another associated autoimmune rheumatic disease were excluded. Six hundred and eighty one patients were included, 95% female, with a mean age of 54.41 years (± 13.70). Sixteen patients presented lymphoma (prevalence: 2.35%, 95% CI: 1.2-3.4%). The average follow-up time was 4.7 years (± 4.94). Six hundread and thirty three patients contributed data for the survival analysis. The incidence rate of lymphoma was 0.54 per 100 patient-years (95% CI: -0,26 a 1,34). The most frequently lymphoma type was MALT. Patients who developed lymphoma had a higher frequency of involvement of most of the domains of the baseline clinical ESSDAI compared to patients who did not present this complication, observing statistically significant differences in glandular (68,75% vs 28.69%, p:0,001), and cutaneous (31.25% vs 10.99%, p: 0.01) domains. The glandular domain of clinical ESSDAI was the main domain associated lymphoma development (H.R: 4.54, 95% CI: 1.57-13.12). Conclusion: This was the first study with data on the population of Argentina about the prevalence of lymphoma in patients diagnosed with Sjogren's syndrome. The prevalence of lymphoma in our cohort was lower than previously published. Despite observing a lower frequency of lymphoma in our study, we found an association with risk markers described in the literature, such as baseline parotidomegaly and cutaneous involvement.

Sjögren's Syndrome, Non-Sjögren's Syndrome, and Graft-Versus-Host Disease Related Dry Eye.

I have reviewed available literature on dry eye related to Sjögren's syndrome (SS), non-Sjögren's syndrome (non-SS), and graft-versus-host disease (GVHD) to examine aqueous tear deficient dry eye as a subtype of dry eye. This section will focus on clinical studies regarding those subtypes of dry eye. I searched the PubMed database from 1990-2017 for discussion of clinical features, diagnostic criteria, and risk factors of SS, non-SS, and GVHD-related dry eye. In addition, therapeutic options for each subtype of dry eye are described. Although the clinical presentations of SS and chronic graft-versus-host disease (cGVHD) are similar, ocular surface fibrotic changes are characteristic of ocular GVHD but not SS- or non-SS-related dry eye. Recently, diagnostic criteria for each disease have been proposed and include the American College of Rheumatology/European League Against Rheumatism (ACR-EULAR) for SS and the International Chronic Ocular GVHD consensus criteria. Although there has been gradual progress, there are currently no specific therapies and few approved treatment options for these intractable diseases, including SS and GVHD. As judged by the findings, these subtypes of dry eye are different clinical entities from simple dry eye. Therefore, novel therapies, specific to these subtypes of dry eye, may be required in the future.

The Parotid Gland in Primary Sjögren Syndrome: Association of Ultrasound, Histopathology and Saliva Production in the Diagnostic Workup

Objectives: The parotid glands are commonly involved in primary Sjogren syndrome (pSS). The aim of this study was to assess the diagnostic accuracy of ultrasound of the parotid glands (PSGUS) compared with parotid histopathology and parotid saliva production. Study Design: We included consecutive patients suspected to have pSS. All patients underwent a full diagnostic workup according to American College of Rheumatology– European League Against Rheumatism (ACR-EULAR) criteria, including PSGUS, parotid gland biopsy, and collection of stimulated parotid saliva. For PSGUS, the average score of hypoechogenic areas in both parotid glands was applied (range 0-3). On hematoxylin and eosin (HE P < .001) and percentage of lymphocytic infiltrate (ρ = 0.575; P < .001). There was a moderate to good absolute agreement between the PSGUS and focus scores (78.5%), plasma cell shift (79.8%), LELs (81.4%), and GCs (82.7%). “Presence of hypoechogenic areas” was not very sensitive to predict focus score (69.2%), plasma cell shift (45.8%), LELs (61.5%), or GCs (34.6%). Interestingly, almost all patients with less than 25% presence of hypoechogenic areas in glandular parenchyma were also negative for GCs (98.7%). A substantial number of these patients did not have a positive focus score (81.4%), plasma cell shift (90.7%), or LELs (87.8%). There was a fair reversed correlation between PSGUS and stimulated parotid saliva flow (ρ = −0.259; P = .07). Conclusions: This is the first study comparing the diagnostic accuracy of PSGUS with histopathology and salivary secretion in detail. PSGUS and histopathology have a stronger association compared with PSGUS and parotid secretion. The specificity of PSGUS increases when the results are compared with plasma cell shift, LELs, and GCs, rather than with the focus score.

PMS4 - RHEUMATOID ARTHRITIS TREATED WITH SIX-MONTHS OF FIRST-LINE BIOLOGIC OR BIOSIMILAR THERAPY: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

In 2016, the French National Authority for Health (Haute Autorité de Santé, HAS) initiated an economic evaluation of biologic disease-modifying anti-rheumatic drugs (boDMARDs) for Rheumatoid Arthritis (RA). Our objective is to present the estimates of the comparative effectiveness of first-line boDMARDS, and their European Medicines Agency approved biosimilars (bsDMARDs), in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses. A systematic literature review was conducted using eight databases, including MEDLINE and EMBASE, up to January 2017. Randomised controlled trials (RCTs) were sought of etanercept (ETN) and its biosimilar, infliximab and its biosimilars, abatacept, adalimumab, certolizumab pegol, golimumab and tocilizumab (TCZ), where data for licensed dose were extracted for each intervention as combination therapy with conventional synthetic (csDMARD) or as monotherapy. Two populations were considered: methotrexate (MTX)-naïve patients with severe active RA (DAS28≥5.1); and moderate-to-severe active RA (DAS28≥3.2) previously treated with csDMARDs. Outcomes were ACR response and EULAR response at 22-30 weeks follow-up. Network meta-analyses (NMA) were conducted using a Bayesian Markov Chain Monte Carlo approach based on a random effects model. Forty-six RCTs met the eligibility criteria of the review. In the MTX-naïve population, MTX plus methylprednisolone was most likely, using median values, to achieve the best ACR response. In the csDMARD-experienced population, the greatest median effects for ACR and EULAR responses were associated with TCZ monotherapy, and the following combination therapies (plus MTX): boDMARD ETN, bsDMARD ETN and TCZ. The MTX-naïve patients NMA demonstrated no superiority for combination boDMARDs over intensive csDMARDs. In csDMARDs-experienced patients, the NMA identified no statistically significant difference between the boDMARDs and bsDMARDs. The estimates of EULAR and ACR responses should be used as short-term effectiveness inputs in the RA economic model comparing the different therapeutic choices for RA treatment in France.