Bone erosions and joint damage caused by chikungunya virus: a systematic review

ABSTRACT Background: Chikungunya fever is an emerging global infection transmitted by Aedes mosquitoes that manifests as an acute febrile illness with joint pain and can lead to chronic arthritis. The mechanism underlying chronic joint damage remains unclear; however, chronic chikungunya arthritis shares similarities with rheumatoid arthritis. Disease-modifying antirheumatic drugs have revolutionized rheumatoid arthritis treatment by preventing joint damage. However, the role of these therapies in chronic chikungunya arthritis has not been determined. We conducted a systematic review to evaluate the burden of joint structural damage in chronic chikungunya arthritis to help to define the role of disease-modifying therapy in this disease. Methods: This systematic review included retrospective and prospective studies, trials, and case reports evaluating joint damage caused by chikungunya virus. Various databases were searched without any date or language restrictions. Study selection was conducted independently by two researchers, and data were extracted from the articles selected. Results: A total of 108 studies were initially evaluated, with 8 meeting the inclusion criteria. Longitudinal studies have reported persistent joint pain from chikungunya infection and the progression of radiographic joint damage up to 13 years post-infection. Joint imaging revealed synovial inflammation, bone erosion, and cartilage destruction in patients with chronic chikungunya arthritis. Conclusions: Few studies have addressed chikungunya-induced joint damage, limiting our understanding of chronic chikungunya arthritis. Nevertheless, chronic chikungunya arthritis has similarities to rheumatoid arthritis. The success of early disease-modifying antirheumatic drug therapy in rheumatoid arthritis underscores the need for comprehensive research on its role in chikungunya arthritis.

Características de los pacientes con artritis reumatoidea que impactan en la satisfacción y la adherencia al tratamiento: subanálisis de los datos de Argentina, Chile y Uruguay del estudio SENSE / Characteristics of patients with rheumatoid arthritis that impact treatment satisfaction and adherence: subanalysis of data from Argentina, Chile and Uruguay from the SENSE study

Introducción: las necesidades y perspectivas de los pacientes son determinantes para tratar la artritis reumatoidea (AR). Objetivos: evaluar el impacto de la respuesta inadecuada a los fármacos antirreumáticos modificadores de la enfermedad (DMARD) sobre la satisfacción con el tratamiento, los resultados y las perspectivas de pacientes adultos con control inadecuado de la AR de actividad moderada/alta. Materiales y métodos: se evaluó la satisfacción mediante el cuestionario Treatment Satisfaction Questionnaire for Medication (TSQM) v1.4. Se recolectaron datos sobre la calidad de vida, la adherencia y las estrategias de manejo. Se presentan los resultados para Argentina, Chile y Uruguay (n=202). Resultados: el promedio de la escala de satisfacción global TSQM fue de 62,3±21,8. El 83% informó buena adherencia. Las principales expectativas del tratamiento fueron "alivio duradero de los síntomas" y "menos dolor articular". El 53,47% prefirió tratamiento oral y el 75,74% eligió un rápido inicio de acción. El efecto secundario menos aceptado fue "mayor riesgo de neoplasias". Se planificó rotar el DMARD en el 55% de los casos. De estos, el 84,7% se consideraron terapias avanzadas. La mayoría estaba abierto a un esquema combinado, pero el 25,2% prefirió no utilizarlo. Conclusiones: los resultados reafirman el compromiso con las estrategias treat-to-target, considerando la individualización de las decisiones terapéuticas en el contexto regional.

Introduction: patients' needs and perspectives are determinants for the treatment of rheumatoid arthritis (RA). Objectives: to evaluate the impact of inadequate response to disease-modifying antirheumatic drugs (DMARDs) on treatment satisfaction, outcomes and perspectives of adult patients with inadequate control of moderate/high activity RA. Materials and methods: satisfaction was assessed using the TSQM v1.4 questionnaire. Data on quality of life, adherence and management strategies were collected. Results are presented for Argentina, Chile and Uruguay (n=202). Results: the mean of the TSQM global satisfaction score was 62.3±21.8. Eighty-three percent reported good adherence. The main expectations of treatment were "lasting relief of symptoms" and "less joint pain". The 53.47% of patients preferred an oral treatment; 75.74% chose a rapid onset of action. The least accepted side effect was "increased risk of malignant neoplasms". Fifty-five percent planned to rotate DMARD. Of these, advanced therapies were considered in only 84.7%. Most were open to a combination treatment, but 25.2% preferred not to use it. Conclusions: the results reaffirm the commitment to treat-to-target strategies, considering the individualization of therapeutic decisions in the regional context.

Effect of biological disease-modifying antirheumatic drugs on body composition in patients with rheumatoid arthritis: a systematic review and meta-analysis.

BACKGROUND: Rheumatoid arthritis (RA) generates an inflammatory profile that predisposes to total and visceral fatty accumulation and reduced fat free mass (FFM). This metabolic disorder contributes to poor functionality, increased cardiovascular risk and higher mortality. This study aimed to address a systematic review with meta-analysis to determine the effect of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) on body composition (BC) of patients with RA. METHODS: The search was conducted at the electronic databases PubMed, Cochrane Library, Embase, Lilacs and grey literature. This investigation was carried until July 2021. Outcomes of interest were total weight, body mass index (BMI), fat mass (FM) and FFM. A meta-analysis comparing these outcomes in RA patients under bDMARD treatment versus controls was performed. RESULTS: Out of 137 studies reviewed, 18 were selected: fifteen prospective cohorts, two retrospective cohorts, and one cross-sectional study. The studies comprised 1221 patients, 778 on bDMARD treatment and 443 controls, which included RA patients under conventional synthetic DMARD (csDMARD). No study addressing BC analysis in patients using tsDMARD was found. The mean age and duration of the disease was 56.7 years and 6.77 years, respectively. Ten studies demonstrated a significant increase of total weight in 88.2% of patients and 42.3% for BMI. In studies that analyzed BC by double X-ray absorptiometry (DXA), the increase in total weight and BMI correlated positively to the increase in FFM. The meta-analysis carried out in five studies showed no significant difference of the mean difference for total weight 0.12 kg (95% CI - 5.58, 5.82), BMI 0.08 kg/m2 (95% CI - 1.76, 1.92), FM - 0.08 kg (95% IC - 5.31, 5.14), and FFM - 2.08 kg (95% CI - 7.37, 3.21). CONCLUSION: This systematic review suggests a possible impact of bDMARDs on BC of RA patients, even though, the meta-analysis carried out in a small part of these studies was not able to confirm significant variation in BC components. TRIAL REGISTRATION: PROSPERO code: CRD42020206949.

Effect of biological disease-modifying antirheumatic drugs on body composition in patients with rheumatoid arthritis: a systematic review and meta-analysis

Abstract Background: Rheumatoid arthritis (RA) generates an inflammatory profile that predisposes to total and visceral fatty accumulation and reduced fat free mass (FFM). This metabolic disorder contributes to poor functionality, increased cardiovascular risk and higher mortality. This study aimed to address a systematic review with meta-analysis to determine the effect of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) on body composition (BC) of patients with RA. Methods: The search was conducted at the electronic databases PubMed, Cochrane Library, Embase, Lilacs and grey literature. This investigation was carried until July 2021. Outcomes of interest were total weight, body mass index (BMI), fat mass (FM) and FFM. A meta-analysis comparing these outcomes in RA patients under bDMARD treatment versus controls was performed. Results: Out of 137 studies reviewed, 18 were selected: fifteen prospective cohorts, two retrospective cohorts, and one cross-sectional study. The studies comprised 1221 patients, 778 on bDMARD treatment and 443 controls, which included RA patients under conventional synthetic DMARD (csDMARD). No study addressing BC analysis in patients using tsDMARD was found. The mean age and duration of the disease was 56.7 years and 6.77 years, respectively. Ten studies demonstrated a significant increase of total weight in 88.2% of patients and 42.3% for BMI. In studies that analyzed BC by double X-ray absorptiometry (DXA), the increase in total weight and BMI correlated positively to the increase in FFM. The meta-analysis carried out in five studies showed no significant difference of the mean difference for total weight 0.12 kg (95% CI − 5.58, 5.82), BMI 0.08 kg/m2 (95% CI − 1.76, 1.92), FM − 0.08 kg (95% IC − 5.31, 5.14), and FFM − 2.08 kg (95% CI − 7.37, 3.21). Conclusion: This systematic review suggests a possible impact of bDMARDs on BC of RA patients, even though, the meta-analysis carried out in a small part of these studies was not able to confirm significant variation in BC components. Trial registration: PROSPERO code: CRD42020206949.

Polymyalgia rheumatica: A case series from Colombia and analysis of Latin America.

OBJECTIVE: Polymyalgia rheumatica (PMR) is the most common inflammatory disease in patients over 50 years. Information about the disease in Latin America (LATAM) is scarce. We aimed to evaluate a group of Colombian patients with PMR and to conduct a systematic review of PMR in LATAM. METHODS: A multicentric retrospective study was performed. Medical records of 256 PMR patients were evaluated. Patients were divided into two groups, those fulfilling the 2012 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for PMR and those who did not (i.e., clinical diagnosis). A systematic literature review and meta regression was performed comparing Colombian vs LATAM patients. RESULTS: From 256 patients, 145 (56.6%) fulfilled the 2012 EULAR/ACR criteria, and 111 (43.3%) were classified by clinical diagnosis. Inflammatory bilateral shoulder pain, pelvic girdle aching, morning stiffness >45 min, elevated erythrocyte sedimentation rate (ESR), and C-reactive protein (CPR), and Methotrexate (MTX) prescription were more common in the 2012 EULAR/ACR group. None of the included patients presented overt polyautoimmunity (PolyA), whereas up to 24% exhibited latent PolyA. In addition, these patients showed high frequency of malignancy (7.59%). In the meta regression analysis, Colombian patients exhibited lower ESR levels, and were less likely to develop giant cell arteritis (GCA) as compared to the rest of LATAM data. CONCLUSION: Patients with PMR in LATAM exhibit similar phenotypes from other cohorts worldwide. Malignancy, GCA and latent PolyA should be considered in the routine clinical follow-up of patients with PMR.

Prevalence of hospital readmissions and related factors in patients with autoimmune diseases.

OBJECTIVE: Autoimmune diseases generate an impact on the morbidity and mortality of patients and are a burden for the health system through hospital admissions and readmissions. The prevalence of readmission of patients with these diseases has not yet been described as a group, but rather as sub-phenotype. The objective of this study is to determine the prevalence of hospital readmissions in a Colombian population with autoimmunity and the factors related to readmission. METHODS: All patients with autoimmune diseases who were evaluated by the rheumatology service and hospitalized between August 2018 and December 2019 at the Fundación Hospital Infantil Universitario De San José de Bogotá were described. A bivariate analysis was done, and three multivariate logistic regression models were built with the dependent variable being readmission. RESULTS: Of the total 199 admissions, 131 patients were evaluated and 32% were readmitted. The most frequent sub-phenotype in both groups (readmission and no readmission) was SLE (51% and 59%). The most frequent cause of hospitalization and readmission was disease activity (68.7% and 64.3%). History of hypertension was associated with readmission (adjusted OR: 2.98-95% CI: 1.15-7.72). In a second model adjusted for confounding variables, no factor was associated. In a third model analyzing the history of kidney disease and previous use of immunosuppressants (adjusted for confounding variables), the previous use of immunosuppressants was related to readmission (OR: 2.78-95% CI 1.12-6.89). CONCLUSION: Up to a third of patients with autoimmunity were readmitted and arterial hypertension was an associated factor. This suggested a greater systemic compromise and accumulated damage in patients who have these two conditions that may favor readmission. A history of immunosuppressant use may play a role in readmission, possibly by increasing the risk of developing infections.

Does current evidence on disease-modifying antirheumatic drugs for psoriatic arthritis reinforce an effect on radiographic progression? Results from a systematic review and meta-analysis.

This study aims to estimate the effect of synthetic and biologic disease-modifying antirheumatic drugs (DMARDs) on radiographic progression and quality of life in adult patients with psoriatic arthritis. A comprehensive search was performed using MEDLINE, Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CCRCT). Clinical trials comparing DMARDs with placebo for ≥ 12 weeks were included. The meta-analysis was conducted with a random-effects model using mean differences (MD). A total of 16 trials with overall moderate quality of evidence were included. Exposure to a biologic agent reduced radiographic progression at 24 weeks of treatment (MD: - 0.66; [95% CI - 0.97 to - 0.34]; P < .00001; I2 = 100%). The reduction of the baseline score was more than two times higher for TNF blockers compared with IL-17 and IL-12/IL-23 inhibitors (MD: - 0.94 vs - 0.41). Improvement in health-related quality of life scores was observed in biologic-treated populations (MD: - 0.21; [95% CI - 0.25 to - 0.18]; P < .00001; I2 = 97%). No sufficient data were available regarding conventional synthetic agents. Our data analyses suggest a better control of radiological damage with bDMARDs, as compared to placebo, after 24 weeks of treatment. However, the accuracy of these results in real life are jeopardized by the exceedingly high level of heterogeneity exhibited within and across included studies, and the true intervention effect cannot be determined with confidence. Further research is required to assess long-term outcomes and to control heterogeneity in the evaluation of treatments for psoriatic arthritis. PROSPERO registration number: CRD42019122223. Key Points • Radiographic progression is not the primary outcome for most efficacy studies in psoriatic arthritis; hence, baseline data are substantially diverse in major clinical trials. • The best available evidence on this particular outcome is currently at a moderate risk of bias. • Existing reports of the effect of DMARDs on structural damage must be taken with caution. • Further research is required to assess long-term outcomes and to control heterogeneity between studies.

Real-life data of survival and reasons for discontinuation of biological disease-modifying drugs 'in' rheumatoid arthritis.

Background Rheumatoid arthritis is a chronic, autoimmune disease in which treatment has evolved with a variety of therapeutic classes. Biological disease-modifying antirheumatic drugs have improved therapy; however, the continued long-term use of these drugs with sustained safety and efficacy remains a challenge. ObjectiveThe objective of this study was to analyze time of use and reasons for discontinuation of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.SettingIt is as part of REAL (Rheumatoid Arthritis in Real Life), a multicenter project that evaluated Brazilian patients with rheumatoid arthritis in a real-life setting. Eleven referral centers for the treatment in the public network participated in the study.MethodsWe conducted a cross-sectional analysis of data collected in the REAL study from August to October 2015 study. The patients were submitted to clinical evaluation and analysis of medical records.Results1125 patients were included (89.5% women; median age: 56.6 years; and disease time: 12.8 years). A total of 406 (36.09%) participants were on a biological disease-modifying antirheumatic drugs. Infliximab was the drug with the longest time of use (12 years). Most (64.4%) drug suspension episodes were due to inefficacy. Adalimumab and certolizumab had a greater number of suspensions due to primary inefficacy, while discontinuations for abatacept were due more to secondary inefficacy. Infliximab had fewer suspensions due to primary inefficacy and golimumab had fewer episodes of secondary inefficacy. Regarding side effects, infliximab was suspended a greater number of times because of clinical and laboratory side effects. Abatacept and adalimumab had fewer suspensions due to clinical side effects, and certolizumab, rituximab and tocilizumab had fewer laboratory adverse effects. Conclusion Among the biological disease-modifying antirheumatic drugs being used for long periods, infliximab had greater time of use. Most drug suspensions (64%) were due to primary or secondary inefficacy. Number of discontinuations due to clinical and laboratory adverse effects for each drug was analyzed, and these data should be confirmed by other real-life studies. Knowledge of what is happening in real life is essential to health professionals, who need to be aware of the most common adverse effects and to health managers, who aim for greater cost-effectiveness in the choice of medications.

Intravenous tocilizumab in the management of rheumatoid arthritis: Clinical practice findings from a 6-month international, multicentre, observational study in Central America and the Caribbean / El tocilizumab intravenoso en el tratamiento de la artritis reumatoide: resultados de la práctica clínica de un estudio internacional, multicéntrico y observacional de 6 meses de duración en América Central y el Caribe

ABSTRACT Tocilizumab (TCZ), an 1interieukin-6 receptor-α Inhibitor, is Indicated in patients with moderate to severe rheumatoid arthritis with inadequate response to disease modifying drugs. ACT UP is a multinational project co11ecting information from severa1 post-marketing TCZ studies. Aim: To determine the proportion of patients in the routine clinical care setting receiving intravenous TCZ after 6 months treatment. Identification of TCZ treatment patterns, efficacy, and safety were also recorded. Method: This prospective non-interventional 6-month study, collected real-world information from 169 Central American and Caribbean patients. No interventional procedures or additional visits outside routine clinical care practice were performed. Statistical analysis was essentially descriptive. Results: Adherence rate was 74.0%, with 97% of patients receiving TCZ as first biological therapy line and there were no deviations from the local label. Almost 85% of patients started with combination therapy, and the majority remained under this scheme throughout the study. A significant decrease in disease activity assessments and acute phase reactants values were detected during TCZ treatment. The percentage of patients that achieved improvement according to the different levels of the American College of Rheumatology (ACR) increased during the study, and relevant enhancements in quality of life were also accomplished. Adverse events (AEs) occurred in 35 patients, with metabolic and nutritional disorders being the most common. Serious AEs were reported in 3% of patients, and special interest AEs occurred in 6 patients. Conclusion: Treatment adherence was mainly determined by follow-up and compliance with the administration schedule. Efficacy analysis showed better results than those reported in international literature. The incidence of AEs was also lower than in previously published data.

RESUMEN El tocilizumab (TCZ) está indicado en la artritis reumatoide moderada a severa, principalmente en respuestas inadecuadas a fármacos convencionales. ACT UP es un proyecto multinacional que recopila información relacionada con varios estudios de poscomercialización. Objetivo: Determinar la proporción de pacientes en la atención clínica de rutina que continúan en tratamiento con TCZ intravenoso después de 6 meses. Se llevó a cabo la identificación de patrones de administración, eficacia y seguridad. Método: Este estudio observacional prospectivo recopiló información de la vida real de 169 pacientes de América Central y el Caribe. No se hicieron intervenciones ni visitas adicionales fuera de la práctica clínica habitual. El análisis estadístico fue esencialmente descriptivo. Resultados: La tasa de adherencia al tratamiento fue del 74,0%, el 97% de los pacientes reci bieron TCZ como primera línea biológica y no existieron desviaciones en las indicaciones de administración según el inserto local. Aproximadamente el 85% de los pacientes inició TCZ como terapia combinada, y la mayoría permaneció bajo este esquema. Se evidenció una dis minución en la actividad de la enfermedad y un aumento en el porcentaje de pacientes que lograron respuesta según los diferentes grados del Colegio Americano de Reumatología. En 35 pacientes se presentaron eventos adversos (EA), siendo los relacionados con metabolismo y nutrición los más comunes. Se informaron EA graves en el 3% de los pacientes y de interés especial en 6 casos. Conclusión: El seguimiento de los pacientes y el cumplimiento del programa fueron los prin cipales determinantes en la adherencia. El análisis de eficacia mostró mejores resultados que los reportados previamente y la incidencia de EA fue menor que en otros estudios.

Peficitinib hydrobromide to treat rheumatoid arthritis.

Peficitinib hydrobromide is a small Janus kinase inhibitor (JAK1, JAK2, JAK3 and TYK2) molecule for the treatment of rheumatoid arthritis (RA). Phase II and phase III clinical trials and extension studies with different doses have been conducted to assess the drug's efficacy and safety with substantially improved outcomes observed in RA. This JAK inhibitor oral drug demonstrated clinical response as once-daily monotherapy in patients with moderate to severe RA, also in combination with methotrexate (MTX), who had an inadequate response to MTX. The findings from studies of this new JAK inhibitor have shown that, both in monotherapy as well as in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), it has efficacy, safety and tolerability in RA patients.

Ultrasound Assessment of Disease Activity Prevents Disease-Modifying Antirheumatic Drug (DMARD) Escalation and May Reduce DMARD-Related Direct Costs in Rheumatoid Arthritis With Fibromyalgia: An Exploratory Study.

OBJECTIVES: as an objective measure, ultrasound (US) could prevent rheumatoid arthritis (RA) overtreatment induced by concomitant fibromyalgia (FM). Our goal was to study how patients with RA and FM who underwent a US examination differed from those without a US examination in terms of overall disease-modifying antirheumatic drug (DMARD) escalation and biologic DMARD-related direct costs. METHODS: Patients with RA and FM were seen between 2011 and 2017. In cases of 28-joint Disease Activity Score (DAS28) overestimation, patients were referred to undergo a US examination. The US group underwent a US examination to confirm disease activity, and the DAS28 group had disease activity assessment based solely on the DAS28. RESULTS: Of 230 patients with RA, 22 women with RA and FM (DAS28 group, n = 9; and US group, n = 13) were seen in 316 visits (115.68 patient-years). The DMARD treatment was escalated in 27.1% of visits in the DAS28 group versus 17.3% in the US group (P = .046). The relative risk of DMARD escalation in the DAS28 group compared to the US group was 1.57 (95% confidence interval, 1.01-2.43). In sum total, US$240,784.52 were spent on biologics throughout the entire study period. Basing biologic DMARD prescriptions on US results could save an average of US$405.66 per patient-year. CONCLUSIONS: In this real-life study of patients with RA and FM, a US examination was associated with less DMARD escalation and could reduce biologic DMARD direct costs. Specifically, synovitis as scored by power Doppler US could be useful as a treatment target for RA in patients with DAS28 overestimation due to FM, but further studies are necessary.

Influence of treatments on cell adhesion molecules in patients with systemic lupus erythematosus and rheumatoid arthritis: a review.

BACKGROUND: Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are autoimmune diseases characterized by changes in cell adhesion molecules (CAMs). OBJECTIVE: To review the influence of the main drugs used in the treatment of SLE and RA on CAM levels. METHODS: A bibliographic search was performed using electronic databases. The research included human studies, in vivo or in vitro, with an experimental or observational design, and with no limit of publication date or number of subjects. Animal studies and non-standard treatments were not considered. RESULTS: We included 21 studies, 3 on SLE and 18 on RA with monotherapy or combined trials. The most used drugs were cyclophosphamide (CY, in 2 studies) and methylprednisolone pulse (pMP, n = 2) in SLE; and methotrexate (MTX, n = 9) and infliximab (IFX, n = 4) in RA. In addition, the most frequently examined CAMs to predict response to treatment were vascular cell adhesion molecule-1 (VCAM-1, n = 2) in SLE, and intercellular adhesion molecule-1 (ICAM-1, n = 12), VCAM-1 (n = 12), and E-selectin (n = 14) in RA. After treatment, CAM levels were decreased in SLE and RA patients with active disease. CONCLUSIONS: It is concluded that the CAM biomarkers may reflect disease activity and the response to treatment in SLE and RA patients.

Detection of Increased Relative Expression Units of Bacteroides and Prevotella, and Decreased Clostridium leptum in Stool Samples from Brazilian Rheumatoid Arthritis Patients: A Pilot Study.

Interactions between gut microbes and disease modifying antirheumatic drugs (DMARDs) have been proposed. The aim of the present study was to evaluate the presence of some specific bacteria in stool samples from Brazilian RA patients receiving DMARDs and correlate these data with diet, clinical parameters, and cytokines. Stool samples were used for gut bacteria evalutation by qPCR. Serum samples were used to quantify IL-4 and IL-10 by flow cytometer. Statistics were performed by Pearson chi-square, Mann-Whitney U test, and Spearman's correlation. The study included 20 RA patients and 30 healthy controls. There were no significant differences (P > 0.05) in dietary habits between RA patients and controls. Concerning gut bacteria, we observed an increase in relative expression units (REU) of Bacteroides and Prevotella species in stool samples from patients, and a decrease in REU of Clostridium leptum when compared with healthy controls. Positive correlation between Prevotella and rheumatoid factor was detected. The IL-4 and IL-10 concentrations were increased in patients when compared with controls. We concluded that gut bacteria are different between RA patients receiving DMARDs and healthy controls. Further studies are necessary to determine the real role of gut microbes and their metabolities in clinical response to different DMARDs in RA patients.

Use of synthetic and biologic DMARDs during pregnancy.

Introduction: Since most of the autoimmune diseases (AID) affect mostly women in their fertile years, and fertility is in general preserved, the use of disease-modifying antirheumatic drugs (DMARDs) during conception, pregnancy, and lactation has been a matter of concern in the treatment of women affected by AID. Areas covered: We performed a comprehensive review of the latest and most relevant research papers published in the field and discussed different aspects related to the use of synthetic and biologic DMARDs and immunosuppressants in the preconceptional period, during pregnancy and lactation in AID patients, both in males and females. Expert commentary: Active AID impose an increased risk for adverse maternal and fetal outcomes, such as preeclampsia, miscarriage, intrauterine growth restriction, prematurity, low birth weight, and stillbirth. Family planning with proper contraception and shared decision-making on the ideal time to conceive with treatment adjustment must be a rule. One of the main challenges when counseling and/or adjusting treatment of patients that are planning a pregnancy is to provide a medication that is at the same time efficacious and safe at the conceptional period and to developing the fetus.

Potential uses of an infodemiology approach for health-care services for rheumatology.

OBJECTIVES: This is a demand-based infodemiology study using the Google Trends and AdWords tools to illustrate infodemiology's potential use in rheumatology. The study investigates three questions in North American countries: (1) What terms associated with "rheumatology" and "arthritis" do people search for on Google? (2) What is the search volume for disease-modifying antirheumatic drugs (DMARDs)? and (3) What is the search volume for the term "arthritis" compared with for "hepatitis C" and "breast cancer"? METHODS: We conducted independent searches by country and search term for 2015-2017. Seventeen DMARDs were searched for 2015 through May 2018, with the turmeric remedy included for comparison. Data were exported to Excel for further analysis, adjusted by country population, and expressed as searches per 100,000 inhabitants (SpTh). RESULTS: There were approximately 550 associated terms for "arthritis" in each country, and 5679 SpTh for DMARDs across the three countries. Searches for turmeric numbered slightly lower than for all DMARDs together in Canada and the USA, but were 70% higher in Mexico. Turmeric was also searched four times more than the most-searched biological DMARD in Canada and the USA, and 60 times more in Mexico. Arthritis was more commonly searched for in Canada than hepatitis C and breast cancer, but hepatitis C was highest in the USA and breast cancer in Mexico. Monthly trends did not show expected peaks associated with arthritis awareness campaigns. CONCLUSION: Infodemiology provides preliminary information that could help in generating hypotheses, assessing health-care interventions, or even in providing patient-centered care.

Serum P-glycoprotein level: a potential biomarker of DMARD failure in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: A cross-sectional study was conducted in 151 RA patients. Patients were classified into two groups according to the response achieved in terms of the disease activity score (DAS)28 after ≥ 6 months: (1) patients with a therapeutic response to DMARDs, with DAS28 < 3.2; and (2) patients without a response to DMARDs, with persistent DAS28 ≥ 3.2. We explored a wide group of clinical factors associated with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk of P-gp elevation as a marker of failure to achieve a therapeutic response to DMARDs was computed using multivariate logistic regression. RESULTS: Serum P-gp levels were significantly higher in RA patients (n = 151) than in the controls (n = 30) (158.70 ± 182.71 ng/mL vs. 14.12 ± 8.97 ng/mL, p < 0.001). The P-gp level was correlated with the DAS28 score (r = 0.39, p < 0.001). RA patients with DMARD failure had higher serum P-gp levels than patients with a therapeutic response (206 ± 21.47 ng/mL vs 120.60 ± 15.70 ng/mL; p = 0.001). High P-gp levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54-7.27, p = 0.001). After adjusting for confounding variables, elevated P-gp remained associated with DMARD failure (OR 2.64, 95% CI 1.29-5.40, p = 0.01). CONCLUSION: Elevated serum P-gp is associated with DMARD failure. The P-gp level can be considered a clinical tool for evaluating the risk of DMARD failure in patients; however, future prospective studies should be performed to evaluate the utility of this marker in predicting long-term responses.

Influence of disease-modifying antirheumatic drugs on oxidative and nitrosative stress in patients with rheumatoid arthritis.

BACKGROUND: Nitro-oxidative stress plays a central role in the pathogenesis of rheumatoid arthritis (RA) and several articles show correlation with disease activity. However, the influence and mechanisms by which disease-modifying antirheumatic drugs (DMARDs) may interfere with nitro-oxidative stress are poorly understood. OBJECTIVE: To show the available data on the effect of the DMARDs on the nitro-oxidative stress in RA patients. METHODS: A bibliographic search was carried out in the electronic databases PUBMED, Lilacs, Scientific Electronic Library Online (SCIELO), and Science Direct and the research was limited to human studies, independently of the publication date. RESULTS: Most studies were performed with infliximab (IFX, 4 articles), tocilizumab (TCZ, 3 articles) and methotrexate (MTX, 2 articles). MTX and leflunomide showed similar results with reduction of nitric oxide. The studies with TCZ verified a marked decrease of reactive oxygen and nitrogen species. Most studies with IFX found a reduction of protein oxidation, evaluated by protein carbonyl measurement. In the present review, the most remarkable results were observed with the increase of the antioxidant defenses through several markers and antioxidant systems. The only study with etanercept showed very similar results to those obtained with MTX, with decreased pentosidine and oxidative DNA damage. CONCLUSIONS: The majority of the studies reported in this work showed an improvement in the redox state, which could be related to success of the therapy. Thus, oxidative and nitrosative stress markers may be useful to early evaluate the response of DMARDs in patients with RA.

Remission-induction therapies for early rheumatoid arthritis: evidence to date and clinical implications.

Recent guidelines on rheumatoid arthritis (RA) point to the importance of achieving remission as soon as possible during the course of the disease. The appropriate use of antirheumatic drugs is critical, particularly in early RA patients, before 24 weeks, since this is a 'window of opportunity' for treatment to modify disease progression. A treat-to-target strategy added to an aggressive therapeutic approach increases the chance of early remission, particularly in early RA patients. We conducted an overview of current therapeutic strategies leading to remission in early RA patients. We also provide interesting predictive factors that can guide the RA management strategy with regard to disease-modifying treatment and/or drug-free remission.

Two-Year Safety and Efficacy Experience in Patients with Methotrexate-Resistant Active Rheumatoid Arthritis Treated with Etanercept and Conventional Disease-Modifying Anti-rheumatic Drugs in the Latin American Region.

BACKGROUND: Although long-term data are available from biologic studies in North American/European populations with rheumatoid arthritis (RA), long-term findings in Latin American RA populations are limited. OBJECTIVE: To examine long-term safety/efficacy of etanercept, methotrexate, and/or other disease-modifying anti-rheumatic drugs (DMARDs) in Latin American patients with moderate-to-severe active RA. METHODS: In the first phase of this open-label study, patients were randomized to etanercept 50 mg weekly plus methotrexate or conventional DMARD (hydroxychloroquine or sulfasalazine) plus methotrexate for 24 weeks. At the start of the second phase (week 24), investigators selected a treatment regimen that included any combination/dosage of etanercept, methotrexate, hydroxychloroquine, or sulfasalazine based on previous treatment response, preference, and local product labeling, and was continued for the 104-week extension. RESULTS: In the extension, in the group previously randomized to etanercept-plus-methotrexate therapy, etanercept was continued in 259/260 patients; methotrexate continued in 260/260; and hydroxychloroquine and sulfasalazine added in 8/260 and 3/260, respectively. In the group previously randomized to conventional DMARD-plus-methotrexate therapy, conventional DMARD was discontinued in 86/126 and etanercept added in 105/126. Among etanercept-exposed patients (total exposure, 798.1 patient-year [PY]), rates of adverse events, serious adverse events, and serious infections per PY were 1.7, 0.07, and 0.02 events per PY. In both groups, after treatment modification was permitted, clinical response rates and improvements in clinical/patient-reported outcomes from baseline were sustained to week 128. CONCLUSION: After investigators were permitted to modify treatment, etanercept was part of the treatment regimen in 95% of patients. Continuation or addition of etanercept in the 2-year extension resulted in a consistently good risk:benefit profile. TRIAL REGISTRATION: Open-Label Study Comparing Etanercept to Conventional Disease Modifying Antirheumatic Drug (DMARD) Therapy; ClinicalTrials.gov, number NCT00848354; https://clinicaltrials.gov/ct2/show/NCT00848354.

Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part II.

BACKGROUND: Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. OBJECTIVES: To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus, rheumatoid arthritis (RA) and antiphospholipid syndrome (APS). METHODOLOGY: Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and staging of recommendations, internal validation by peers and external validation of the final document. The quality criteria of the AGREE II instrument were followed. RESULTS: The panels answered 37 questions related to maternal and fetal care in lupus erythematosus, RA and APS, as well as for use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. In this second part, the recommendations for pregnant women with RA, APS and the use of antirheumatic drugs during pregnancy and lactation are presented. CONCLUSIONS: We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with RA and APS integrate the best available evidence for the treatment and follow-up of patients with these conditions.