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Psoriatic arthritis is a chronic systemic inflammatory disease that affects the skin, musculoskeletal structures and other organs and systems compromising functionality, quality of life and reducing the life expectancy of patients. It is a complex disease that requires specialist and timely care and management. The alternatives for treating the manifestations of psoriatic arthritis have increased and the effect of the different agents on specific manifestations has been clarified in recent studies. Therefore, we should incorporate the available evidence to build a strategy for the treatment of these patients. The Mexican College of Rheumatology selected a committee to evaluate these different alternatives and make recommendations. Methods The study group included 16 rheumatologists and 3 certified dermatologists, selected from different health institutions and regions of the country. An executive committee was formed to coordinate the meetings and a committee of experts selected the literature search criteria, prepared the research questions, rated the quality of the evidence, and produced the recommendations in the different disease domains based on the GRADE methodology. Results 24 updated recommendations were generated for the treatment of patients with psoriatic arthritis. The recommendations establish the role of the drugs currently available in our country. The importance of adequate disease control is emphasized, individualizing the level of involvement of each patient in each of the six domains potentially affected by the disease. In addition, the sequence in the choice of treatments available for each domain is established, based on their efficacy, safety profile and accessibility. Conclusions With this consensus document, it will be possible to improve the care of patients with psoriatic arthritis. The recommendations were generated based on the best available information and in consideration of the Mexican health system.

BackgroundDetermining potential predictors of clinical response would allow a more personalized rheumatoid arthritis (RA) treatment approach in heterogeneous populations such as Latin American (LA) patients.MethodsPost hoc analysis to identify baseline characteristics predictive of clinical remission in response to treatment with etanercept (ETN) plus methotrexate (MTX) in LA patients with moderate to severe MTX-resistant RA. We report data from the group of patients who received ETN 50 mg/week plus MTX (ETN + MTX,n = 281) in a clinical trial consisting of an initial 24-week open-label phase, followed by a 104-week extension. Remission was defined as 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) score ResultsAt Week 24 and Week 128, 27% (66/241) and 42% (91/219) of patients in the ETN + MTX group achieved remission. On average, patients achieving remission were younger and had lower baseline ESR, lower Physician Global Assessment (PGA) scores, lower total Health Assessment Questionnaire (HAQ) scores, and lower visual analog scale (VAS) Pain scores compared with patients who did not achieve remission. The best subset of baseline variables predicting Week 24 remission in the stepwise regression model were age ≤ 49 years (odds ratio [OR] 2.93), body mass index (BMI) > 28.5 kg/m2(OR 3.24), disease duration > 3.7 years (OR 2.22), ESR ≤ 42 mm/h (OR 2.72), PGA ≤ 6 (OR 3.21), tender joint count ≤ 14 (OR 2.25), and total HAQ score ≤ 1.6 (OR 2.86). At Week 128, age ≤ 42 years (OR 2.21), SF-36 Mental Health Scale score > 39.6 (OR 2.16), White race (OR 4.07), > 18 swollen joints (OR 2.11), and VAS Pain ≤ 41 (OR 6.05) at baseline were the best subset of significant predictors of remission.ConclusionsIn LA patients with RA, younger age, higher BMI, longer disease duration, higher SF-36 Mental Health Scale score, higher swollen joint count, and overall lower disease activity predicted clinical response to ETN + MTX therapy.Trial registration: ClinicalTrials.gov Identifier: NCT00848354.

DBA/1 mice arthritis models have contributed to our understanding of human rheumatoid arthritis (RA) and spondyloarthritis (SpA) pathogenesis, as well as the exploration of therapeutic targets for treatment. Quantitative polymerase chain reaction (qPCR) is an indispensable tool in molecular research, which requires reference gene validation to obtain consistent and reliable results.To determine the stability of candidate reference genes for qPCR in the joint of collagen-induced arthritis (CIA) and spontaneous arthritis (SpAD) DBA/1 mice.The expression of eleven commonly used reference genes (ACTB, B2M, EF1a, GAPDH, HMBS, HPRT, PPIB, RPL13A, SDHA, TBP, and YWHAZ) was assessed by qPCR and the data were compared using delta-Ct methods and the geNorm, NormFinder, and RefFinder software packages. Genes identified as stable in each model were used for the quantification of inflammatory cytokines RESULTS: The gene stabilities differed between the two arthritis models in the DBA/1 mice. EF1a and RPL13A were the best reference genes for SpAD, while RPL13A and TBP were the best for the CIA. These genes allowed the data normalization for the quantification of the inflammatory cytokines in both models; these results showed an increase in the expression of IL-1B, IL-12B, IL-17A, and IL-6 in the inflamed joints. The use of different primer sequences for the same reference gene resulted in different relative quantification values.This study demonstrates that commonly used reference genes may not be suitable for arthritic tissues from DBA/1 mice, and strengthening the principle that meticulous validation of reference genes is essential before each experiment to obtain valid and reproducible qPCR data for analysis or interpretation.

Background The Janus kinase inhibitor upadacitinib is a potential treatment for psoriatic arthritis. The efficacy and safety of upadacitinib as compared with adalimumab, a tumor necrosis factor a inhibitor, in patients who have an inadequate response to nonbiologic disease-modifying antirheumatic drugs are unclear. Methods In a 24-week, phase 3 trial, we randomly assigned patients in a 1:1:1:1 ratio to receive oral upadacitinib at a dose of 15 mg or 30 mg once daily, placebo, or subcutaneous adalimumab (40 mg every other week). The primary end point was an American College of Rheumatology 20 (ACR20) response (>20% decrease in the number of tender and swollen joints and >20% improvement in at least three of five other domains) at week 12 with upadacitinib as compared with placebo. Secondary end points included comparisons of upadacitinib with adalimumab. Results A total of 1704 patients received an active drug or placebo. The percentage of patients who had an ACR20 response at week 12 was 70.6% with 15-mg upadacitinib, 78.5% with 30-mg upadacitinib, 36.2% with placebo (P

Spondyloarthritis (SpA) is a group that includes a wide spectrum of clinically similar diseases manifested by oligoarticular arthritis and axial or peripheral ankylosis. Although axial SpA is predominant in Caucasians and adult-onset patients, juvenile-onset and Latin American patients are characterized by severe peripheral arthritis and particularly foot involvement. The peripheral involvement of SpA can vary from tarsal arthritis to the most severe form named ankylosing tarsitis (AT). Although the cause and etiopathogenesis of axSpA are often studied, the specific characteristics of pSpA are unknown. Several animal models of SpA develop initial tarsitis and foot ankylosis as the main signs, emphasizing the role of foot inflammation in the overall SpA spectrum. In this review, we attempt to highlight the clinical characteristics of foot involvement in SpA and update the knowledge regarding its pathogenesis, focusing on animal models and the role of mechanical forces in inflammation.

Objective To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors (TNFi).

Objectives Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized efficacy and safety of tofacitinib in Mexican patients from RA Phase 3 and long-term extension (LTE) studies. Methods Data from Mexican patients with RA and an inadequate response to disease-modifying antirheumatic drugs (DMARDs) were taken from four Phase 3 studies (pooled across studies) and one open-label LTE study of tofacitinib. Patients received tofacitinib 5 or 10 mg twice daily, adalimumab (one Phase 3 study) or placebo (four Phase 3 studies) as monotherapy or in combination with conventional synthetic DMARDs. Efficacy up to Month 12 (Phase 3) and Month 36 (LTE) was assessed by American College of Rheumatology 20/50/70 response rates, Disease Activity Score (erythrocyte sedimentation rate), and Health Assessment Questionnaire-Disability Index. Safety, including incidence rates (IRs; patients with events/100 patient-years) for adverse events (AEs) of special interest, was assessed throughout the studies. Results 119 and 212 Mexican patients were included in the Phase 3 and LTE analyses, respectively. Tofacitinib-treated patients in Phase 3 had numerically greater improvements in efficacy responses versus placebo at Month 3. Efficacy was sustained in Phase 3 and LTE studies. IRs for AEs of special interest were similar to those with tofacitinib in the global and Latin American RA populations. Conclusions In Mexican patients from the tofacitinib global RA program, tofacitinib efficacy was demonstrated up to Month 12 in Phase 3 studies and Month 36 in the LTE study, with a safety profile consistent with tofacitinib global population.

Background/Aims Upadacitinib (UPA) is a JAK inhibitor under evaluation for PsA treatment. We aimed to assess efficacy and safety of UPA vs placebo (PBO) and adalimumab (ADA) in patients with prior inadequate response (IR) or intolerance to ≥ 1 non-biologic DMARD. This research was previously presented at EULAR; published in Annals of Rheumatic Diseases. Methods Patients with active PsA (≥3 swollen, ≥3 tender joints), active/historical psoriasis, ≤2 non-bDMARDs were randomized 1:1:1:1 to once-daily UPA 15mg (UPA15), UPA 30mg (UPA30), ADA 40mg every other week, or PBO. Primary endpoint: proportion of patients achieving ACR20 for UPA vs PBO at Wk12. Secondary endpoints: change in HAQ-DI, FACIT-F, SF-36-PCS (Wk12), sIGA of Psoriasis 0/1, PASI75, change in Self-Assessment of Psoriasis Symptoms (Wk16), change in modified Sharp/van der Heijde Score (mTSS), proportion patients achieving MDA, resolution of enthesitis (LEI=0) and dactylitis (LDI=0) (Wk24), non-inferiority and superiority vs ADA for ACR20, superiority for HAQ-DI, patient assessment of pain NRS (Wk12). Additional secondary endpoints: ACR50/70 at Wk12 and ACR20 at Wk2. Treatment-emergent adverse events (TEAEs) through Wk24 reported for patients receiving ≥1 dose of study drug. Results 1,705 patients were randomised; 1,704 received study drug (mean age 50.8 yrs, mean duration of PsA diagnosis 6.1 yrs). 82% on ≥ 1 concomitant non-bDMARD. At Wk12, ACR20 rates were 70.6% with UPA15 and 78.5% with UPA30 vs 36.2% with PBO (p < 0.001 for UPA15/30 vs PBO) and 65.0% with ADA (non-inferiority, p < 0.001 for UPA15/30 vs ADA; superiority, p < 0.001 for UPA30 vs ADA). More patients achieved ACR50/70 with UPA15/30 vs PBO and UPA30 vs ADA. Improvements were observed with UPA15/30 vs PBO for all secondary endpoints and for UPA 15/30 vs ADA for HAQ-DI and UPA30 vs ADA for improvement in pain. At Wk24, change in mTSS was 0.25 for PBO, -0.04 for UPA15, 0.03 for UPA30, and 0.01 for ADA (p < 0.001 for UPA15/30 vs PBO). Rates of TEAEs and serious AEs, including serious infections, were similar in PBO, UPA15, and ADA arms and higher with UPA30. Herpes zoster rates were similar for PBO and UPA15/30. No MACE was reported with UPA. One malignancy occurred in both the PBO and UPA15 arms; 3 malignancies were reported in both UPA30 and ADA arms. VTE were reported in 1 PBO patient, 1 UPA30 patient and 2 ADA patients. One death occurred in the PBO arm. Conclusion In this non-bDMARD-IR PsA population UPA15/30 demonstrated improvement in musculoskeletal symptoms, psoriasis, physical function, pain, fatigue and inhibited radiographic progression; improvements observed by Wk2. At Wk12, UPA15/30 were non-inferior to ADA for ACR20, with superiority demonstrated for UPA30. Greater percentages of UPA vs PBO patients achieved stringent disease control measures (MDA, ACR50/70, sIGA 0/1). No new safety signals were identified compared to the safety profile observed in RA. Disclosure I. McInnes: Other; I.McI has received research grants and honoraria from Abbvie, BMS, Celgene, Novartis Lilly, Janssen, Pfizer, UCB. J. Anderson: Shareholder/stock ownership; J.A. may be a stock/ shareholder of AbbVie Inc. M. Magrey: Consultancies; M.M. has received consulting fees from Novartis, Eli Lilly, Pfizer, and Janssen. Grants/research support; M.M. has received grants/ research support from Amgen, AbbVie, and UCB Pharma. J.F. Merola: Consultancies; J.F.M. is a consultant for Merck, Abbvie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and Leo Pharma. Y. Liu: None. M. Kishimoto: Consultancies; M.K. has received consulting fees from AbbVie, Eli Lilly, Celgene, Pfizer, Gilead, Janssen, and UCB Pharma. Honoraria; M.K. has received honoraria/ speakers fees from AbbVie, Eisai, Celgene, Pfizer, Novartis, Eli Lilly, Tanabe-Mitsubishi, Ayumi, Janssen, Astellas, and UCB Pharma. S. Jeka: None. C. Pacheco-Tena: None. X. Wang: Shareholder/stock ownership; X.W. may be a shareholder of AbbVie Inc. L. Chen: Shareholder/stock ownership; L.C. may be a stock/shareholder of AbbVie Inc. P. Zueger: Shareholder/stock ownership; P.Z. may be a stock/shareholder of AbbVie Inc. A. Pangan: Shareholder/stock ownership; A.P. may be a stock/shareholder of AbbVie Inc. F. Behrens: Honoraria; F.B. has received honoraria and speakers fees from Pfizer, AbbVie, Sanofi, Lilly, Novartis, UCB, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai. Grants/research support; F.B. has received grants/ research support from Pfizer, Janssen, Chugai, Celgene and Roche.

Aims To assess the effect of physical exercise (PE) on the histological and transcriptional characteristics of proteoglycan-induced arthritis (PGIA) in BALB/c mice. Methods Following PGIA, mice were subjected to treadmill PE for ten weeks. The tarsal joints were used for histological and genetic analysis through microarray technology. The genes differentially expressed by PE in the arthritic mice were obtained from the microarray experiments. Bioinformatic analysis in the DAVID, STRING, and Cytoscape bioinformatic resources allowed the association of these genes in biological processes and signalling pathways. Results Arthritic mice improved their physical fitness by 42.5% after PE intervention; it induced the differential expression of 2,554 genes. The bioinformatic analysis showed that the downregulated genes (n = 1,371) were significantly associated with cellular processes that mediate the inflammation, including Janus kinase-signal transducer and activator of transcription proteins (JAK-STAT), Notch, and cytokine receptor interaction signalling pathways. Moreover, the protein interaction network showed that the downregulated inflammatory mediators interleukin (IL) 4, IL5, IL2 receptor alpha (IL2rα), IL2 receptor beta (IL2rβ), chemokine ligand (CXCL) 9, and CXCL12 were interacting in several pathways associated with the pathogenesis of arthritis. The upregulated genes (n = 1,183) were associated with processes involved in the remodelling of the extracellular matrix and bone mineralization, as well as with the processes of aerobic metabolism. At the histological level, PE attenuated joint inflammatory infiltrate and cartilage erosion. Conclusion Physical exercise influences parameters intimately linked to inflammatory arthropathies. Research on the effect of PE on the pathogenesis process of arthritis is still necessary for animal and human models. Cite this article: Bone Joint Res. 2020;9(1):36–48.

Physical exercise (PE) is recommended for Rheumatoid Arthritis (RA), but the molecular and biological mechanisms that impact the inflammatory process and joint destruction in RA remain unknown. The objective of this study was to evaluate the effect of PE on the histological and transcriptional changes in the joints of adjuvant-induced arthritis (AIA) rat model. AIA rats were subjected to PE on a treadmill for eight weeks. The joints were subjected to histological and microarray analysis. The differentially expressed genes (DEGs) by PE in the arthritic rats were obtained from the microarray. The bioinformatic analysis allowed the association of these genes in biological processes and signaling pathways. PE induced the differential expression of 719 genes. The DEGs were significantly associated with pathogenic mechanisms in RA, including HIF-1, VEGF, PI3-Akt, and Jak-STAT signaling pathways, as well as response to oxidative stress and inflammatory response. At a histological level, PE exacerbated joint inflammatory infiltrate and tissue destruction. The PE exacerbated the stressed joint environment aggravating the inflammatory process, the hypoxia, and the oxidative stress, conditions described as detrimental in the RA joints. Research on the effect of PE on the pathogenesis process of RA is still necessary for animal models and human.

The aim of the study was to describe the oral health and orofacial function of Mexican patients with rheumatoid arthritis (RA) and their association with clinical and radiological aspects of the disease. Patients with RA received a complete odontological exam, which also included a clinical and radiographic assessment of the temporomandibular joint (TMJ). The rheumatologic assessment included detailed profiling of the disease and serological and radiographic parameters. The study included 62 RA patients; the median (min–max) age was 51 (18–72) years old and 8.5 (1–39) years of disease duration. The 63.6% of the patients had DAS28 ≥ 3.2, and a median (min–max) of Sharp/van der Heijde score (SvdHS) of 41 (0–214). 98.3% of the patients presented caries, which were severe in 53.3% of the cases. The 73.8% of the patients were missing teeth due to caries, with a median (min–max) of 4 (0–32) teeth missing per patient. Oral hygiene was classified as bad in 49.1% of patients and only 15.3% of them had a healthy periodontium. The TMJ function was abnormal in 98.4% of the patients and 62.9% of them presented moderate or severe TMJ disorder (TMD). The radiographic damage of the TMJ correlated positively with the SvdHS. No correlations were found between disease activity or structural progression and orofacial variables, including periodontitis. There are severe oral and orofacial health problems in RA patients despite having medical attention for their disease. Multidisciplinary management remains an area of opportunity for both the medical specialists and the health system in our country.

Objectives To assess efficacy & safety of intravenous golimumab in pediatric patients with active polyarticular course juvenile idiopathic arthritis despite methotrexate therapy through 28 weeks of treatment. Methods A multicenter, Phase 3, single arm, open-label trial was conducted using intravenous golimumab at a dose of 80mg/m2 given at weeks 0 & 4, then every 8 weeks thereafter, in pediatric patients ages 2-17 years old with active polyarticular course juvenile idiopathic arthritis despite methotrexate therapy. Patients received commercial MTX weekly at same BSA-based dose as at time of study entry. All the results below are based on full analysis set which includes all patients who received at least 1 dose of study agent. Results 180 patients were screened (130 enrolled, 127 treated) with the first patient screened on 22Dec2014; last patient first treated 26Dec2017, & last patient’s Wk28 visit was 09Jul2018. Proportion of JIA ACR 30,50,70, & 90 responders at Wk28 was 83.5%,79.5%,70.1%, & 46.5%, respectively. 29.1% of patients met criteria for inactive disease at Wk28. Median change from baseline for JASDAS 10, 27, & 71 was -14.20, -16.60, & -20.32, respectively at Wk28. JADAS 10, 27, & 71 minimal disease activity was met by 15% of patients at Wk28. Proportion of patients experiencing at least 1 treatment-emergent AE through Wk28 was 77.2%. MedDRA system organ class with highest incidence of AEs was Infections & infestations (57.5%);most commonly reported AE upper respiratory tract infection(17.3%), then nasopharyngitis(15.0%).Six patients experienced serious AEs through Wk28: Herpes zoster disseminated, Infective exacerbation of bronchiectasis, Sepsis, Varicella, Mycosis fungoides, & Suicidal ideation. These events resulted in permanent discontinuation of intravenous golimumab, except for Varicella. Conclusion Intravenous golimumab delivered at a dose of 80mg/m2 at weeks 0 & 4, then every 8 weeks thereafter and appears to be effective in these patients with a safety profile similar to other TNF inhibitor therapies. Disclosure of Interests Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus (

Background Rheumatoid arthritis (RA) and periodontal disease are inter-related conditions. However, factors predictive of periodontal disease progression in patients with early rheumatoid arthritis (eRA) are lacking. The aim of this study was to identify factors associated with the progression of clinical attachment loss (CAL) in interproximal dental sites of eRA patients. Methods Twenty-eight eRA patients were evaluated for the progression of CAL at 280 interproximal dental sites at 1 year of follow-up. Markers of RA activity (rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein), a marker of bone resorption (Dickkopf-related protein 1), Disease Activity Score 28 and Simple Disease Activity Index were included as potential systemic predictive factors. Plaque index, gingival index, pocket depth, clinical attachment level and Dickkopf-related protein 1 in crevicular fluid at baseline were included as potential local predictive factors. Data were analysed in a hierarchical structure using generalised linear mixed models for progression at each site (> 2 mm) during follow-up. Results C-reactive protein level was the most important predictive systemic factor for the progression of CAL. The mean CAL and a high degree of gingival inflammation in interproximal sites at baseline were important predictive local factors (p p Conclusions Systemic factors, including RA disease activity and baseline periodontal condition, were associated with periodontal progression. Pharmacological treatment may affect periodontal progression in patients with early RA.

Background Rheumatic diseases (RDs) represent a global problem for health care systems and patients. Community Oriented Program for Control of Rheumatic Diseases (COPCORD) is a low-cost screening tool for detecting musculoskeletal (MSK) pain and RDs. Objective The aim of this study was to examine the pattern of MSK pain and RDs in clinic population in Chihuahua City, Mexico. Methods A cross-sectional study was conducted in 7 primary health clinics using the COPCORD methodology in subjects older than 18 years. People with MSK pain not induced by trauma (positive cases) were evaluated by primary care physicians and rheumatologists. Results The study included 1006 individuals with a mean age of 46.0 (SD, 15.8) years; 751 (74.7%) were women. Musculoskeletal pain in the previous 7 days was reported by 571 individuals (56.75%; 95% confidence interval [CI], 53.8%-60.1%), and 356 cases (35.4%; 95% CI, 32.5%-38.4%) were COPCORD positive. The mean pain intensity in visual analog scale was 6.62 (SD, 2.4). The most common painful joint was the knee (54.7%; 95% CI, 51.1%-59.0%). Two hundred eighty subjects with MSK pain (49.0%) previously sought medical attention, and 375 (65.7%) were under treatment. Functional impairment was reported by 69.8% of the COPCORD-positive subjects. The prevalence of RDs was 21.4% (95% CI, 18.9%-23.8%). The most prevalent disease was osteoarthritis (10.3%; 95% CI, 8.6%-12.4%), followed by regional pain syndromes (5.5%; 95% CI, 4.1%-7.0%), rheumatoid arthritis (1.4%; 95% CI, 0.8%-2.2%), and mechanical low-back pain (1.4%; 95% CI, 0.7%-2.2%). Conclusions Musculoskeletal pain is an important problem that affects our community. The data provided in this study will be presented to the local authorities to help in the development of prevention strategies.

Background An association between Rheumatoid arthritis(RA) and Periodontal Disease(PD) has been reported. However, predicting factors of PD progression in patients with eRA are lacking Objectives To establish the predictive factors for progression of PD in patients with eRA including clinical and serological active scores of RA and status of PD Methods This cohort study evaluated the progression of PD at 280 inter-proximal dental sites in 28 patients within 2 years of diagnosis with eRA and they were evaluated to establish their progression through one year of follow-up. Adult patients were classified according to the 2010 ACR and the EULAR criteria. Periodontal diagnosis was established based on the AAP and the CDC and Prevention criteria. Serum markers of RA (rheumatoid factor, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and anticitrullinated protein antibodies (APCAs) were evaluated, disease activity was assessed by disease activity score (DAS28-ESR) AND the simplified disease activity index (SDAI). Plaque index, gingival index, pocket depth, and clinical attachment loss (CAL) were evaluated at baseline and at one year follow-up. Data were analysed to establish predictive generalised linear mixed models (GLMM) for clinical attachment loss progression at each site with ≥2 or≥3 mm CAL Results The patients included had an average age of 47.5±12.69 and 75% were women. The comorbidity given by the habit of smoking actively occurred only in 1% of patients. The 35.71% had levels of ESR >20 mm3/h and 39% APCA positive while in 60.71% had CRP ≥3 mg/L and 67.86% of patients had a positive FR. Regarding the indices of activity of the disease, DAS28-PCR>2.6 was found in 67.86% of the patients and SDAI scale >3.3 in 75%. 71.43% of the patients were being treated with DMARD and corticoid therapy. 71.43% of patients had a diagnosis of periodontitis. CAL≥2 mm and ≥3 mm was observed at 15% and 7.5% of dental sites, respectively. Factors associated with CAL in dental sites were: age, ESR, RF, DAS28, treatment with DMARD-Corticoids, periodontal pocket, CAL and percentage of CAL>5 mm, plaque index, gingival index and haemorrhage. Variables RA associated with activity such as CRP, DAS28, and SDAI showed a similar behaviour and they were more frequently associated in periodontal progressive sites. The principal predictive periodontal factors were the percentage of sites with CAL>5 mm and high gingival inflammation at baseline. Patients receiving combined treatment with disease-modifying antirheumatic drugs (DMARD) and corticosteroids exhibited less CAL. The predictive values of the GLMM for CAL of ≥3 and≥2 mm were 98% and 82%, respectively Conclusions Systemic factors as disease activity score and serum biomarkers such as baseline periodontal status are associated with periodontal disease progression in early RA patients. It is known that the very low daily dose prednisolone in combination DMARD therapy substantially decreased radiographic progression and it could influence periodontal disease progression too in patients with RA in early stages of the disease Reference [1] Bello-Gualtero JM,et al.J Periodontol.2016;87:346 Disclosure of Interest None declared

Background The ASAS-HI is a new instrument based in the International Classification of Functioning, Disability and Health to assess the impact of axSpA; ASAS-HI has been validated in Mexican patients. Objectives To investigate the status of health in Mexican patients with axSpA using the ASAS-HI Methods This is multicenter, cross-sectional study of 377/423 patients with axSpA (ASAS criteria) referred by 64 rheumatologists with private or institutional practice across the country in a period of six months. Sociodemographic and clinical data were collected at each site and analysed centrally. Results The ASAS imaging arm were fulfilled 87.5% and the clinical by 61.8%; HLA-B27 was positive in 80.1%; 71.6% were males; 51.9% received bDMARDs. Mean ages at onset and diagnoses were 25.8 (9.9) and 32.8 (11.7) years; median age was 41.6 (13.7) years. The correlation between ASAS-HI and BASDAI, BASFI, and EQ-5D was significant. ASAS-HI mean score was 6.4 (4.2); the cut off was six; values below six meant good health, which corresponded to 203 (53.84%) patients. Univariate analysis disclosed significant differences between groups in variables that were significant in the regression models (see below) and in health care coverage, enthesitis, joint counting, glucocorticoids, HLA-B27, sacroiliitis, BASMI, and ASDAS. In the multivariate analysis, two models were associated ASAS-HI: 1) sex, education, comorbidities, joint surgery, and physician global assessment; 2) BASDAI, BASFI, and EQ-5D Conclusions ASAS-HI cut off of six identified good health in 46.15% of patients with axSpA. ASAS-HI correlated with other measures of disease activity, functioning, and quality of life. In multivariate analysis, ASAS-HI associated with those measures as we all as with demographic and clinical variables. References [1] Kiltz U, van der Heijde D, Cieza A, Boonen A, Stucki G, Ustun B, et al. Developing and validating an index for measuring health in patients with ankylosing spondylitis. Rheumatology (Oxford). 2011;50(5):894–8. [2] Kiltz U, van der Heijde D, Boonen A, Bautista-Molano W, Burgos-Vargas R, Chiowchanwisawakit P, et al. Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set: translation and cross-cultural adaptation into 15 languages. RMD Open. 2016;2(2):e000311. Acknowledgements We acknowledge 64 rheumatologists (grupo sacroiliacos) all over the country that participated in the study Disclosure of Interest None declared

To characterize the orofacial abnormalities in patients with rheumatoid arthritis (RA) and compare them with those in a reference population.The study included 30 RA patients and 30 consecutive patients in an odontology clinic in whom RA was ruled out. Patients underwent a clinical dental examination which included: 1) clinical and radiographic abnormalities of the temporomandibular joint; 2) biomechanical craniocervical analysis; 3) state of dentition and treatment needs; 4) periodontal status; 5) oral hygiene status; and 6) facial pain, which was compared among study groups. In addition, the association between the variables studied was determined through correlation tests.Patients with RA showed a higher prevalence of temporomandibular abnormalities, both clinical (100.0% vs. 60.0%, P.001) and radiographic, including erosions (50.0% vs. 16.0%, P=.010), compared with individuals in the control group. Likewise, patients with RA had a greater number of missing teeth (6.9±5.7 vs. 3.0±2.0, P=.001), more caries (13.4±5.4 vs. 4.9±6.5, P=.001), periodontitis (1.3±0.9 vs. 0.8±0.8, P=.015), poorer oral hygiene (43.3% vs. 13.3%, P=.005) and greater facial pain (66.7% vs. 20.0%, P.001). The cephalometric analysis of Rocabado showed differences in the craniocervical angle and hyoid triangle between RA and controls. Significant correlations were obtained between oral and temporomandibular abnormalities.Patients with RA showed a greater orofacial deterioration, which reflects the importance of multidisciplinary care, including periodic dental examination.

Objective.To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA).Methods.The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported.Results.Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96–8.58), infection 38.60 (36.24–41.12), serious infection 1.68 (1.35–2.07), malignancies 1.09 (0.84–1.42), and autoimmune disorders 1.33 (1.05–1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study.Conclusion.These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.

Objective To assess the efficacy and safety of decernotinib (VX-509), an oral selective inhibitor of JAK-3, in patients with rheumatoid arthritis (RA) in whom the response to methotrexate treatment was inadequate. Methods In this 24-week, double-blind, randomized phase IIb study, 358 patients with active RA received either placebo (n = 71) or VX-509 at dosages of 100 mg/day (n = 71), 150 mg/day (n = 72), 200 mg/day (n = 72), or 100 mg twice daily (n = 72). Primary measures of efficacy at week 12 were the response rate according to the American College of Rheumatology 20% improvement criteria (ACR20) and change from baseline in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP). Results At week 12, the ACR20 response rates were 46.5%, 66.7%, 56.9%, and 68.1% in the groups receiving VX-509 at dosages of 100 mg/day, 150 mg/day, 200 mg/day, and 100 mg twice daily, respectively, and 18.3% in the placebo group (P < 0.001 for all comparisons). At week 12, the mean change from baseline in the DAS28-CRP was significantly greater in each VX-509 group compared with the placebo group (P < 0.001). Improvements were maintained at week 24, as shown by the ACR20, ACR50, and ACR70 response rates and mean change from baseline in the DAS28-CRP. The most common adverse event in the VX-509 group was headache (8.7%), and elevated levels of transaminases, lipoproteins, and creatinine were observed. Conclusion VX-509 significantly improved the signs and symptoms of RA at weeks 12 and 24 compared with the placebo group when it was administered in combination with methotrexate. Safety signals included infection and increases in liver transaminase and lipid levels.

The danger model was proposed by Polly Matzinger as complement to the traditional self-non-self- (SNS-) model to explain the immunoreactivity. The danger model proposes a central role of the tissular cells’ discomfort as an element to prime the immune response processes in opposition to the traditional SNS-model where foreignness is a prerequisite. However recent insights in the proteomics of diverse tissular cells have revealed that under stressful conditions they have a significant potential to initiate, coordinate, and perpetuate autoimmune processes, in many cases, ruling over the adaptive immune response cells; this ruling potential can also be confirmed by observations in several genetically manipulated animal models. Here, we review the pathogenesis of rheumatic diseases such as systemic lupus erythematous, rheumatoid arthritis, spondyloarthritis including ankylosing spondylitis, psoriasis, and Crohn’s disease and provide realistic approaches based on the logic of the danger model. We assume that tissular dysfunction is a prerequisite for chronic autoimmunity and propose two genetically conferred hypothetical roles for the tissular cells causing the disease: (A) the Impaired cell and (B) the paranoid cell. Both roles are not mutually exclusive. Some examples in human disease and in animal models are provided based on current evidence.

Background Rheumatoid arthritis (RA) and periodontal disease (PD) have similar underlying pathologic processes and share a general deregulation of the inflammatory response. Objectives To evaluate PD markers in first-degree relatives (FDR) of consanguinity individuals of patients with rheumatoid arthritis to compared with controls and to establish an association to rheumatic activity according to age groups Methods 201 FDR individuals and 201 matched controls were included. Clinical evaluation of rheumatologic and periodontal condition was performed. P. gingivalis,P. gingivalis IgG1 and IgG2, ESR, CRP, RF, ACPAs, painful and swollen joints were assessed. A frequencies analysis, comparisons and a logistic regression model were made. The study was approved by local ethics committee. Results 37.3% of patients with overweight and 10.1% obsesses. Subjects with more than one swelling joint were 21 subjects 30, where 81.8% had periodontitis p=0.006. Regression analysis on the whole group shows a risk to present BMI>25 (OR 1.67 IC-95% 1.02 – 2.74 p=0.042), ACPAs (OR 3.7 IC-95% 1.34–10.22 p=0.012), at least one pain join (OR2.51 IC-95% 1.42–4.44 p=0.001) and gingival index (OR4.57 IC-95% 1.76–11.80 p=0.002) in FDR individuals. Based on age the risk to develop PD was increasing: individuals among 30 to 40 years shows OR 2.76 (IC-95% 1.24–6.18, p=0.013); among 41 to 50 years, OR 4.72 (IC-95% 1.81–12.32, p=0.001); and for >50 years individuals an OR 6.22 (IC-95% 2.55–15.1, p=0.0001). The discriminating analysis by age rank shows that FDR individuals 50 years (n=53) show high risk to present BMI>25 (OR 4.00 IC-95% 1.46–10.45 p=0.007). Conclusions Obesity, ACPA and periodontitis can be considered as relevant conditions associated with the development of RA in FDRs. However, the analysis based on age group shows that periodontal markers do not appear early in FDR individuals; however, clinical rheumatologic variables are manifested and maintained over time. References Bello-Gualtero JM et al. J Periodontol 2016;87:346–356. Disclosure of Interest None declared

Objectives To determine the impact of individual and regional variables on the geographic distribution of RD across six Latin-American countries Methods This is a secondary multilevel analysis of cross-sectional data of COPCORD studies that investigated the prevalence of RD in Argentina, Colombia, Ecuador, Mexico, Peru, and Venezuela. Individual factors were sex, age, comorbidities, job status, and Health Assessment Questionnaire (HAQ) score. Contextual level variables were country and subject9s identification as indigenous. RD predictors, including individual and regional variables, particularly indigenous status were identified with logistic regression models. The effect of contextual variables was estimated with median odds ratio9s (OR) estimation. Results Most individuals included in this analysis came from urban areas (82.40%); their mean age was 43.12 years (95% CI 43.01–43.35); and 56.0% were women. Nearly all of them reported >1 comorbidity (94.70%) and 72.19% were economically active. The prevalence of any RD varied from 1.55% in Peru to 26.09% in Argentina. The mean prevalence of Rheumatoid Arthritis (RA) was 1.58 (range 0.64 to 2.47) (table 1). Aside comorbidities, individual level variables associated to any RD were sex (OR: 1.35; 95% CI 1.28–1.43), age (OR: 1.02; 95% CI 1.01 -1.03), and HAQ score (OR: 3.71; 95% CI 3.22–4.28). Crude comparisons showed significant variations among countries (p Conclusions There common factors associated to the prevalence of RD in the region, however, the estimation of its impact varies in significant way across countries and related to the fact of belong to an indigenous group indicating an increase in the estimated ORs. Acknowledgements National Council for Science and Technology (CONACYT);Colegio Mexicano de Reumatologia (Mexico). EsSalud (Peru). Universidad de Cuenca (Ecuador).ASOREUMA (Colombia). Federico Wilhelm Agricola Foundation (Argentina). PDVSA East, SUELOPETROL and Bristol-Myers Laboratory (Venezuela) Disclosure of Interest None declared

Therapeutic advances in rheumatoid arthritis require periodic review of treatment guidelines. Objective To update the Mexican College of Rheumatology guidelines on the pharmacological treatment of rheumatoid arthritis. Method Board certified rheumatologists from different health institutions and regions of the country participated. Work teams were formed that reviewed the previous guidelines, elaborated new questions, reviewed the literature, and scored the evidence that was presented and discussed in plenary session. The conclusions were presented to infectologists, gynaecologists and patients. Recommendations were based on levels of evidence according to GRADE methodology. Results Updated recommendations on the use of available medications for rheumatoid arthritis treatment in Mexico up to 2017 are presented. The importance of adequate and sustained control of the disease is emphasised and relevant safety aspects are described. Bioethical conflicts are included, and government action is invited to strengthen correct treatment of the disease. Conclusions The updated recommendations of the Mexican College of Rheumatology on the pharmacological treatment of rheumatoid arthritis incorporate the best available information to be used in the Mexican health care system.

Objective To evaluate effects of the anti-interleukin-6 receptor monoclonal antibody sarilumab administered with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on patient-reported outcomes (PROs) in the TARGET trial in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitors (TNF-IR). Methods 546 patients (81.9% female, mean age 52.9 years) were randomised to placebo, sarilumab 150 or 200 mg subcutaneously every 2 weeks + csDMARDs. PROs included patient global assessment (PtGA); pain and morning stiffness visual analogue scales; Health Assessment Questionnaire Disability Index (HAQ-DI); Short Form-36 Health Survey (SF-36); FACIT-Fatigue (FACIT-F); Work Productivity Survey-Rheumatoid Arthritis (WPS-RA) and Rheumatoid Arthritis Impact of Disease (RAID). Changes from baseline at weeks 12 and 24 were analysed using a mixed model for repeated measures; post hoc analyses included percentages of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores ≥ normative values. Results Sarilumab + csDMARDs doses resulted in improvements from baseline at week 12 vs placebo + csDMARDs in PtGA, pain, HAQ-DI, SF-36 and FACIT-F that were maintained at week 24. Sarilumab improved morning stiffness and reduced the impact of RA on work, family, social/leisure activities participation (WPS-RA) and on patients9 lives (RAID). Percentages of patients reporting improvements ≥MCID and ≥ normative scores were greater with sarilumab than placebo. Conclusions In patients with TNF-IR RA, 150 and 200 mg sarilumab + csDMARDs resulted in clinically meaningful patient-reported benefits on pain, fatigue, function, participation and health status at 12 and 24 weeks that exceeded placebo + csDMARDs, and were consistent with the clinical profile previously reported. Trial registration number NCT01709578; Results.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease whose pathogenic mechanisms remain to be elucidated. The oxidative stress and antioxidants play an important role in the disease process of RA. The study of oxidants and antioxidants biomarkers in RA patients could improve our understanding of disease pathogenesis; likely determining the oxidative stress levels in these patients could prove helpful in assessing disease activity and might also have prognostic implications. To date, the usefulness of oxidative stress biomarkers in RA patients is unclear and the evidence supporting them is heterogeneous. In order to resume and update the information in the status of oxidants and antioxidants and their connection as biomarkers in RA, we performed a systematic literature search in the PubMed database, including clinical trials published in the last five years using the word combination “rheumatoid arthritis oxidative stress”. In conclusion, this review supports the fact that the oxidative stress is an active process in RA pathogenesis interrelated to other better known pathogenic elements. However, some controversial results preclude a definite conclusion.

Spondyloarthritis comprise a group of inflammatory rheumatic diseases characterized by its association to HLA-B27 and the presence of arthritis and enthesitis. The pathogenesis involves both an inflammatory process and new bone formation, which eventually lead to ankylosis of the spine. To date, the intrinsic mechanisms of the pathogenic process have not been fully elucidated, and our progress is remarkable in the identification of therapeutic targets to achieve the control of the inflammatory process, yet our ability to inhibit the excessive bone formation is still insufficient. The study of new bone formation in spondyloarthritis has been mostly conducted in animal models of the disease and only few experiments have been done using human biopsies. The deregulation and overexpression of molecules involved in the osteogenesis process have been observed in bone cells, mesenchymal cells, and fibroblasts. The signaling associated to the excessive bone formation is congruent with those involved in the physiological processes of bone remodeling. Bone morphogenetic proteins and Wnt pathways have been found deregulated in this disease; however, the cause for uncontrolled stimulation remains unknown. Mechanical stress appears to play an important role in the pathological osteogenesis process; nevertheless, the association of other important factors, such as the presence of HLA-B27 and environmental factors, remains uncertain. The present review summarizes the experimental findings that describe the signaling pathways involved in the new bone formation process in spondyloarthritis in animal models and in human biopsies. The role of mechanical stress as the trigger of these pathways is also reviewed.

To determine the rate and factors associated with ankylosing spondylitis in a cohort of patients with undifferentiated spondyloarthritides (SpA).62 consecutive patients with undifferentiated SpA seen between 1998 and 1999 underwent clinical and imaging evaluations throughout follow up. The main outcome measure was a diagnosis of ankylosing spondylitis.50 patients with peripheral arthritis (n = 35) and inflammatory back pain (n = 24) (26 male; mean (SD) age at onset, 20.4 (8.8) years; disease duration 5.4 (5.7) years) were followed up for 3-5 years. At baseline,90% of patients had axial and peripheral disease, while 38% had radiographic sacroiliitis below the cut off level for a diagnosis of ankylosing spondylitis (BASDAI 3.9, BASFI 2.9). At the most recent evaluation, 21 patients (42%) had ankylosing spondylitis. Two factors were associated with a diagnosis of ankylosing spondylitis in multivariate analysis: radiographic sacroiliitis grade2 bilateral, or grade3 unilateral (odds ratio (OR) = 11.18 (95% confidence interval, 2.59 to 48.16), p = 0.001), particularly grade 1 bilateral (OR = 12.58 (1.33 to 119.09), p = 0.027), and previous uveitis (OR = 19.25 (1.72 to 214.39), p = 0.001). Acute phase reactant levels, juvenile onset, and HLA-B27 showed a trend to linkage with ankylosing spondylitis (NS).Low grade radiographic sacroiliitis is a prognostic factor for ankylosing spondylitis in patients originally classified as having undifferentiated SpA. Low grade radiographic sacroiliitis should be regarded as indicative of early ankylosing spondylitis in patients with undifferentiated SpA.

Rheumatoid arthritis (RA) is considered an autoimmune disease, but the notion that the process may be triggered by an unknown infectious agent has been a longstanding concept in the pathogenesis of RA. After several decades searching for such causative agents in the joints, the direct evidence is still missing. In the June issue of Arthritis Care & Research, Chen et al provided new insights in this area searching with gas chromatography-mass spectrometry (GC-MS) for muramic acid, a component derived from bacterial cell walls, in the joint tissues of RA patients (1). In the case of reactive arthritis (ReA), infectious agents triggering joint inflammation have been well established (2,3). Gastrointestinal infections by enteric bacterial strains, such as Yersinia, Salmonella, Campylobacter, and Shigella species, and urogential infections by Chlamydia species are known to be associated with ReA. One of the strongest links is the demonstration of Chlamydial DNA in the joints of patients with post-Chlamydia ReA by polymerase chain reaction (PCR) (4,5). However, after a prolonged search for bacterial DNA in RA joints, it remains unresolved whether or not an organism or its antigenic fragments persist locally in these joints. It may still be argued that the causative agent is present at such a low concentration that it cannot be detected with current microbiology techniques. To date, many methods have been used in hunting for microbes in joints with RA, as well as those with ReA, ankylosing spondylitis, and osteoarthritis (OA) (Table 1). In their study, Chen et al screened for bacteria in joint tissues of RA patients using a sensitive pan-bacteria PCR, which can detect DNA of almost any bacterial species. However, no bacterial DNA was found in their study. Despite the absence of bacterial DNA, they probed for evidence of the bacterial cell wall, which represents the major constituent of bacteria. The skeleton of bacterial cell walls mainly consists of polysaccharide, peptidoglycan, and cell wall-associated proteins. Peptidoglycan is the major constituent of the gram-positive bacterial cell wall, whereas lipopolysaccharide (LPS) is the dominant component of the gram-negative bacterial cell wall. The schematic structure of the gram-positive bacterial cell wall is shown in Figure 1. In the current study, Chen et al selected muramic acid, a component of the peptidoglycan moiety of the bacterial cell wall. Muramic acid is unique to bacteria and is not present in the mammalian proteome, making it an ideal chemical marker for detecting bacteria (6). Chen et al detected muramic acid by using a GC-MS with a chemical ionization method sensitive enough to detect even picogram amounts (2 pg/injected amount). GC-MS has previously been used successfully to detect muramic acid in joints of septic arthritis patients) (7,8). Chen et al were able to demonstrate the presence of muramic acid in the joints of some RA patients, suggesting persistence of bacterial cell wall components, rather than bacterial DNA, in the joints of chronic RA (duration more than 5 years). Their findings are in line with earlier reports that bacterial cell wall components were present in RA joints by immunohistochemistry, using an antibody against bacterial cell wall peptidoglycan (9). However, this current study makes the important observation that the presence of bacterial cell wall components is not specific for RA, since they were also found in joint tissues of OA patients. The question has remained open how these bacterial cell wall components might play a biologic role if they persist in the joints for prolonged periods. Are they pathogenic? Several studies have implicated bacterial cell wall components as having multiple immunologic activities that may contribute to joint inflammation. 1) The recently discovered receptors of the first line of host defense—the Tolllike receptors (TLR)—recognize a range of microbes and their products. For example, TLR2 recognizes bacterial peptidoglycan (10). 2) Bacterial peptidoglycan is capable of stimulating synovial macrophages to express the costimulatory molecules CD80 and CD86, and to produce proinflammatory cytokines such as tumor necrosis factor and interleukin 6 (11). 3) Certain bacterial cell walls are able to induce experimental arthritis in rats with histopathologic features resembling RA (12,13). 4) Small fragments of the arthritogenic bacterial peptidoglycan, such as muramyl peptides, possess potent proinflammatory capacity (14). All these lines of evidence suggest that the bacterial cell wall components are potential arthritogenic Xiang Zhang, MD, PhD, Robert D. Inman, MD: University Health Network and University of Toronto, Toronto, Ontario, Canada; Cesar Pacheco-Tena, MD, MSc: Hospital Central Universitario, Universidad Autonoma de Chihuahua, and Hospital Clinica del Parque, Mexico. Address correspondence to R. D. Inman, MD, Arthritis Center of Excellence, ECW 8-005, Toronto Western Hospital, 399 Bathurst Street,Toronto, ON, M5T 2S8 Canada. Submitted for publication December 11, 2002; accepted December 22, 2002. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 49, No. 4, August 15, 2003, pp 479–482 DOI 10.1002/art.11186 © 2003, American College of Rheumatology

Objective: To investigate the role of HLA-B and HLA-DR genes as contributors to genetic susceptibility and clinical expression of the spondyloarthropathies (SpA) in the Mexican population. Methods: The study included 172 patients with SpA (undifferentiated SpA 83, ankylosing spondylitis (AS) 64, and reactive arthritis 25) and 99 healthy controls. The HLA-B and HLA-DR alleles were detected by the polymerase chain reaction with sequence-specific primers technique. Patient assessment included demographic data, diagnostic categories, and disease patterns. Statistical methods included the Mantel-Haenzel χ2 test, Fisher's exact test, and Woolf method for odds ratio (OR). Differences of continuous variables between HLA allele groups were calculated by Student's t test. Results: Increased frequencies of HLA-B27 (pCh10-3, OR=28.7), HLA-DR1 (pC=0.045, OR=2.77), and HLA-B15 (p=0.034, pC=NS, OR=2.04) alleles in the whole group were found. HLA-B27 strength of association (OR) was 41.4 in AS; 20.9 in undifferentiated SpA; 27.2 in reactive arthritis. HLA-DR1 and HLA-B15 were increased in undifferentiated SpA (pC=0.045, OR=2.98 and p=0.004, pC=NS, OR=2.75). By analysing 58 HLA-B27 negative patients it was found that HLA-B15 and HLA-DR1 associations with SpA were independent of HLA-B27; increased frequencies of HLA-B15 were found in the whole SpA group and in patients with undifferentiated SpA (pC=0.03, OR=3.09 and pCh0.01, OR=3.77) and of HLA-DR1 in the latter (p=0.04, pC=NS, OR=3.15). HLA-B27 positive patients were younger than HLA-B27 negative patients at onset (p=0.03), but HLA-DR1 positive patients were older than HLA-DR1 negative patients (p=0.03). Bath indices for disease activity and functioning were higher in HLA-B27 positive patients (p=0.006 and p=0.004 v HLA-B27 negative patients). In contrast, neither HLA-DR1 nor HLA-B15 influenced these indices. Conclusion: Apart from HLA-B27, there is a significant association of HLA-DR1 and HLA-B15 with SpA in Mexicans which is independent of B27. HLA-B27 is associated with younger age at onset and increased disease severity and HLA-DR1 with older age at onset. The strength of HLA-B15, HLA-B27, and HLA-DR1 associations varied in different forms of SpA.

Objective: To investigate the role of HSP70 genes as contributors to genetic susceptibility of the spondyloarthropathies (SpA) in the Mexican population. Methods: The study included 150 patients with SpA (undifferentiated spondyloarthropathy (uSpA) 68, ankylosing spondylitis (AS) 60, and reactive arthritis 22) and 158 healthy controls. HSP70-1, HSP70-2 and HSP70-hom genotypes were analysed by the polymerase chain reaction-restriction fragment length polymorphism technique. Statistical methods included the Mantel-Haenzel, χ2, Fisher's exact test, and Woolf's method for odds ratio (OR). Results: HSP70-2 B/B genotype frequency was increased in the whole group of patients with SpA (pC

Objective To compare the efficacy of 2 low-dose oral methotrexate (MTX) schedules in maintaining remission in patients with rheumatoid arthritis (RA). Methods Patients with RA were included if they were receiving treatment with weekly MTX for at least 9 months and the RA was in remission (defined by American College of Rheumatology [ACR] criteria) for at least 6 months. Patients were stratified by treatment and randomly assigned to weekly or every-other-weekly (EOW; reducing their monthly dose by half) treatment with MTX. Patients were evaluated by a rheumatologist (blinded to the treatment schedule) at baseline and at 6, 12, and 24 weeks. The evaluations included joint counts, Ritchie Articular Index, Health Assessment Questionnaire Disability Index, physician's and patient's global health assessments, visual analog scale for pain, and incidence of adverse effects. Laboratory evaluations were done at baseline and at week 24. Results Fifty-one patients were included (26 taking weekly MTX, 25 taking EOW MTX). Baseline comparisons showed no differences between the groups. The mean duration of RA was 90% of the patients in both groups continued in remission. Evaluations of disease activity at 6 and 12 weeks showed no between-group differences. EOW MTX patients who experienced relapse were switched back to weekly MTX, and after a few weeks, their RA was again controlled. The incidence of adverse effects was slightly higher in the weekly MTX group, although the difference did not reach statistical significance. The observed laboratory values were very similar for both groups, except for the serum aspartate aminotransferase and alanine aminotransferase levels, which decreased in the EOW MTX group and were statistically significant at week 24 (P = 0.04 and P = 0.006, respectively). Conclusion EOW MTX represents a valid therapeutic alternative for a specific subgroup of RA patients, as outlined by the ACR remission criteria. Patients with a short disease duration who were treated early after disease onset with weekly MTX and who achieve sustained remission have a higher probability of success with the EOW MTX schedule.

Juvenile-onset spondyloarthropathies (SpA) are a group of HLA-B27–associated clinical conditions, syndromes, and diseases of the entheses and synovium of the joints, tendon sheaths, and bursae that predominantly involve the lower extremities of children sometimes having enteric or genital infections as triggers, spondylitis and sacroiliitis throughout the course of the disease, or a wide spectrum of extra-articular features. 27 As a whole, juvenile-onset SpA are strongly related to their adult counterparts; however, certain clinical differences at onset make the application of criteria developed for adult onset SpA inappropriate for children. 6,50,98,189 In contrast, the role of HLA-B27 and bacteria, the clinical expression, anatomic substrate, histopathologic nature of lesions, and the treatment are the same or similar for childhood-onset and adult-onset SpA. The recognition of these forms and their clinical differences from juvenile rheumatoid arthritis (JRA) have given juvenile-onset SpA a notorious relevance among childhood arthritides. 1,29,63,85,89,159,169,182 Pediatric and adult rheumatologists have become familiar with juvenile-onset SpA in recent years. Their interest is now expanding from clinical to basic and therapeutic research. The scope of this review includes the analysis of data derived from such research as seen from the work and concepts we have been developing for a number of years.

Multicentric reticulohistiocytosis (MRH) is a rare multisystem, granulomatous debilitating disease. It affects the skin with a nodular diffuse dermatitis and the joints with a severe, potentially deforming, and handicapping arthritis. No standardized therapy exists, it is a disease with heterogeneous severity, and therefore, a diversity of therapeutic responses has been published.Current experience with anti-tumor necrosis factor agents in disease-modifying antirheumatic drug-refractory MRH cases is encouraging, and other agents such as bisphosphonates have proven effective as well. Histological analysis of the granulomatous inflammatory lesions have shown the presence of cytokines including tumor necrosis factor α, interleukin 1, and interleukin 6; the presence of the latter makes tocilizumab a plausible alternative.In this article, we report a 35-year-old woman with MRH refractory to a combined scheme of prednisone and methotrexate, both at high doses, and who received tocilizumab achieving remission on both cutaneous and articular symptoms. Our patient markedly improved by the second infusion (8 mg/kg monthly), and after 9 infusions, she remained asymptomatic; no toxicity was detected. Tocilizumab could be an alternative for disease-modifying antirheumatic drug-refractory MRH.

Objective: To assess the relationship between disease activity and signs and symptoms of infection in Mexican patients with spondyloarthropathies (SpA). Methods: A cross sectional study of 95 non-selected patients with SpA (62 men; mean age 26.4 years), who were examined for signs and symptoms of infection and their association with disease activity. 52 had ankylosing spondylitis (AS), 32 undifferentiated SpA (uSpA), 6 chronic reactive arthritis (ReA), and 5 psoriatic arthritis (PsA). Categorical data were analysed by x 2 or Fisher’s tests. Results: 53 (56%) patients had infections: 41 (43%) upper respiratory tract (URT), 34 (36%) enteric, and 20 (21%) genitourinary infections. More infections occurred in HLAB27 positive patients as a whole (39 v 5; p = 0.003) and in uSpA (12 v 2; p = 0.005). In AS and uSpA, infections occurred in ,50%. 30/39 (77%) patients with active disease (group A) and 23/56 (41%) (group B) (p = 0.001) had infection. There were more enteric infections in group A (47%; p,0.001) and more URT infections in group B (52%; p = NS). 22/30 (73%) patients attributed disease activity to infection. Conclusion: Enteric, and less commonly, URT infections in Mexican patients with SpA, particularly those who were HLAB27 positive, seem to have a role in the active phase of AS and uSpA.

Background Clinical remission is an important treatment goal in rheumatoid arthritis (RA) and is associated with improved physical function and quality of life.1,2 In the phase 3 TARGET study (NCT01709578), sarilumab (150 or 200 mg subcutaneously every 2 weeks + conventional synthetic disease-modifying antirheumatic drugs [csDMARDs]) demonstrated efficacy in adults with active, moderate-to-severe RA and inadequate response to tumor necrosis factor (TNF) inhibitors.3 Infections, neutropenia, injection site reactions, and increased transaminases were among the most common treatment-emergent adverse events.3 Objectives This analysis assessed the proportions of patients achieving clinical remission measured by 4 different disease activity measures in a difficult-to-treat patient population with active RA and inadequate response or intolerance to ≥1 prior TNF inhibitor(s). Methods Four definitions of remission were used: 28-joint disease activity score by C-reactive protein (DAS28-CRP) Results Baseline demographic and disease characteristics were balanced among the 3 treatment groups. At week (wk) 12 and wk 24, the proportion of patients achieving DAS28-CRP Conclusions Sarilumab induced remission (using a broad range of definitions) as early as 12 weeks after initiation of therapy in patients with an inadequate response to TNF inhibitors. Patients with remission generally had improvements in physical function and fatigue as well. References Smolen et al. Ann Rheum Dis. 2014;73:492–509. Radner et al. Arthritis Res Ther. 2014;16:R56. Fleischmann et al. Presented at: ACR; November 7–11, 2015; San Francisco, CA. Acknowledgement This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial assistance was provided by Kristi Porter, PhD, MedThink SciCom, and funded by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interest G. Burmester Grant/research support from: AbbVie, Pfizer, Roche, and UCB, Consultant for: AbbVie, BMS, Pfizer, Merck, MedImmune, UCB, and Roche, Speakers bureau: AbbVie, BMS, Pfizer, Merck, UCB, and Roche, P. Hrycaj: None declared, C. Pacheco-Tena Consultant for: BMS, Janssen, Pfizer, Roche, and UCB, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, Y. Lin Shareholder of: Sanofi, Employee of: Sanofi, D. Bauer Shareholder of: Sanofi, Employee of: Sanofi, J. Fay Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Parrino Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, A. Kivitz Shareholder of: Sanofi and Regeneron Pharmaceuticals, Inc., Consultant for: Sanofi, Pfizer, Roche, and UCB

To evaluate the role of tumor necrosis factor-alpha (TNF-alpha) gene as susceptibility marker for spondyloarthritis (SpA), two polymorphisms (-238 and -308 positions) were analyzed in 229 patients with SpA (113 with ankylosing spondylitis [AS], 92 with undifferentiated SpA [U-SpA], 24 with reactive arthritis), and 169 ethnically matched healthy control subjects. The HLA-B alleles were detected by PCR-SSP technique and the TNF-alpha polymorphism by PCR-RFLP. In comparison with healthy control subjects, the frequencies of TNF-238 in SpA were similar. In contrast, the analysis of -308 polymorphism showed increased frequencies of the T2(A) allele in the whole SpA group (p0.05, pC = NS, OR = 1.83) as well as the T2(A) allele (pC0.05, OR = 2.4) and T1T2(AG) genotype (p0.05, pC = NS, OR = 2.25) in U-SpA patients. Comparison of B27-negative patients and healthy control subjects yielded similar results. There was no significant correlation between TNF genotypes and clinical data. The present study demonstrates that TNF-alpha -308 polymorphism appears to be associated with the genetic susceptibility U-SpA. The association seems independent of the susceptibility conferred by the HLA-B27 in this group of patients.

To evaluate the role of LMP (low molecular weight protein) genes as susceptibility markers for spondyloarthritis (SpA), LMP gene polymorphisms were analyzed in 223 Mexican patients with SpA (81 undifferentiated SpA [U-SpA], 117 with ankylosing spondylitis [AS], 25 with reactive arthritis) and in 139 ethnically matched healthy individuals. LMP genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The LMP2 and LMP7 allele frequencies were similar in patients and healthy controls. Genotype analysis revealed an increased frequency of LMP2 R/R genotype in the whole group of SpA (pC = 0.003, OR = 2.06, 95%CI = 1.3-3.25) and in the clinical subgroups of AS (pC = 0.039, OR = 1.88, 95%CI = 1.1-3.22) and U-SpA (pC = 0.003, OR = 2.56, 95%CI = 1.37-4.8) compared with healthy controls. Analysis in the LMP7 did not reveal significant differences in patients and healthy controls. The HLA-B27-negative AS subgroup also showed an increased frequency of LMP2 R/R genotype (pC = 0.027, OR = 4.81, 95%CI = 1.21-22.13). The LMP2-R/R AS patients were younger than LMP2-H/R and H/H patients at onset of the disease (16.0 +/- 6.8 years for R/R, 22.0 +/- 11.2 years for H/R and 28.6 +/- 10.9 years for H/H) (p0.05). The data suggest that, besides HLA-B27, LMP2 genotypes are also involved in the genetic susceptibility to develop AS in Mexicans. Furthermore, the age at onset of this disease might also be influenced by genotypes of this gene.

Objective: To develop and test an index to evaluate the radiographic changes that occur in the tarsus and adjacent areas of the foot in patients with spondyloarthropathies (SpA). Methods: The spondyloarthropathy tarsal radiographic index (SpA-TRI) was developed in three consecutive steps: (a) detection of descriptors after reviewing 70 radiographic files; (b) descriptor gradation and subsequent modifications performed by a consensus committee, and (c) interobserver variability assessed by three blinded and independent observers on 272 radiographs: anteroposterior 118, lateral 90, oblique 64 from 121 patients with SpA, and intraobserver variability on 75 radiographs from 25 patients with SpA. Statistical analysis included percentage of agreement and κ test. SpA-TRI score ranges from 0 to 4 (0=normal; 1=osteopenia or suspicious findings; 2=definite joint space narrowing, bony erosion(s), periosteal whiskering, or enthesophyte(s) in the plantar fascia or Achilleal tendon attachments; 3=para-articular enthesophyte(s); 4=bony ankylosis (joint space fusion or complete bridging)). Results: Complete agreement for every evaluation was >40%, and discordance >1 grade was

BACKGROUND—Because serious adverse reactions to allopurinol have been related to a reduce creatinine clearance rate and prolonged half life of oxypurinol, it has been recommended that the dose should be adjusted according to the rate of creatinine clearance. However, in some patients with gout the dose is not sufficient to reduce serum levels of uric acid (⩽390 µmol/l) and to halt disease progression. OBJECTIVE—To determine the prevalence of adverse reactions attributable to allopurinol in patients with primary gout according to dose and creatinine clearance rate. METHODS—Data on 120 patients with gout receiving allopurinol, in whom the starting dose was adjusted according to creatinine clearance rate and later increased in some patients to control the disease, were retrospectively reviewed. Two groups were compared: group A, 52 patients receiving creatinine clearance adjusted maintenance doses of allopurinol and group B, 68 patients receiving non-adjusted higher maintenance doses of allopurinol. RESULTS—During follow up 57% required higher allopurinol doses than those recommended according to their creatinine clearance rate. Only five (4%) of 120 consecutive patients developed allopurinol related adverse reactions: four minor skin reactions and one allopurinol hypersensitivity syndrome (AHS). Three of these (including the case of AHS) occurred in group A and two in group B (p=NS). The duration of allopurinol treatment was the same in both groups (group A: 2.3 (3.3) years; group B: 3.7 (4.8) years). No patient in group A, but 44% in group B had a creatinine clearance rate of

Background Although there is much discussion regarding when to initiate a biological agent in rheumatoid arthritis (RA) patients, data on when to stop these agents is scant. Disease activity outcomes after the ending of an industry sponsored clinical trials may provide useful information regarding the duration of drug-free remission for a given biological agent. Objectives To assess the length of remission and rate of relapse of disease activity after ending the open label, long-term extension study (5 yrs) using tocilizumab in RA patients enrolled in the OPTION trial. Methods Patients who no longer received tocilizumab because of the ending of the extension study (5 yrs) of the OPTION trial were analyzed. All patients were: a) in remission (DAS28 Results Forty patients were analyzed, 85% females with a mean age of 53.5 yrs. During the first 12 months of follow-up, 21 (52.5%) patients continued in remission. Relapses occurred in 19 (47.5%) patients, 11 (58%) of them during the first three months after the last tocilizumab administration. No variables were identified to predict length of remission. Conclusions Long-term remission is possible in a substantial number of RA patients after suspension of tocilizumab. Additional data are required to support recommendations for discontinuing a biological agent after achieving remission. These recommendations would impact in patients’ safety and the economic burden imposed by these treatments. References Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 2008;371:989–97. Disclosure of Interest None Declared

This study aimed to determine the prevalence of musculoskeletal (MSK) pain and rheumatic diseases in the Raramuri population (also known as Tarahumaras) who are an indigenous group in the northern state of Chihuahua in Mexico. We used the Community-Oriented Program for Control of Rheumatic Diseases (COPCORD) methodology. An analytical cross-sectional study was conducted including indigenous Raramuri aged ≥18 years from communities settled in Chihuahua City. Subjects with positive MSK pain were evaluated by primary care physicians and rheumatologists. Demographic and occupational factors such as gender and job type associated with rheumatic disease were investigated. A total of 380 indigenous Raramuri (mean age 33.6 ± 13.1 years; 37.9 % male) were interviewed. Seventy-six individuals (20 %) reported MSK pain in the last 7 days. Pain intensity was reported as “severe” and “the most severe” in 30 % of the cases. Fifty-six individuals (14.7 %) reported pain in the past and 86 (22.6 %) had either past or current pain. The prevalence of rheumatic diseases was 10.5 %. Diagnosed diseases were osteoarthritis (6.6 %), low back pain (1.6 %), spondyloarthritis (0.8 %), rheumatoid arthritis (0.5 %), non-specific arthritis (0.5 %), rheumatic regional pain syndromes (0.3 %), and fibromyalgia (0.3 %). Rheumatic disease was associated with the following variables: age (odds ratio (OR) 1.04, 95 % confidence interval (CI) 1.02–1.08; p = 0.006), family history of rheumatic symptoms (OR 6.9; 95 % CI 2.6–18.7; p < 0.001), and Health Assessment Questionnaire-Disability Index (OR 28.9; 95 % CI 2.8–289.7; p < 0.001). A high prevalence of non-traumatic MSK pain suggests the need for a rheumatic disease prevention program in the Raramuri people in Chihuahua, Mexico.

Alterations in tissue oxygen pressure contribute to a number of diseases, including rheumatoid arthritis (RA). Low partial pressure of oxygen, a condition known as hypoxia, is a relevant feature in RA since it is involved in angiogenesis, inflammation, apoptosis, cartilage degradation, energy metabolism, and oxidative damage. Therefore, alterations in hypoxia-related signaling pathways are considered potential mechanisms of disease pathogenesis. The objective of this review is to highlight and update our current knowledge of the role of hypoxia in the pathogenesis of RA. We describe the experimental evidence that RA synovial tissue exists in a hypoxic state, as well as the origin and involvement of synovial hypoxia in different aspects of the pathogenic process.