Vacunación contra el SARS-CoV-2 en pacientes paraguayos con artritis reumatoide

Introducción: La vacunación en poblaciones expuestas a mayor riesgo de enfermedad grave y muerte consecuentes a la infección por SARS-CoV-2, ha generado un gran impacto en la salud pública mundial. Indudablemente, el beneficio ha sido evidenciado mayormente en personas con comorbilidades crónicas, donde la artritis reumatoide (AR) juega un rol importante. Objetivo: Analizar la vacunación contra Sars-CoV-2 en pacientes paraguayos con AR, durante la pandemia COVID-19. Métodos: Se realizó un estudio multicéntrico, en el que se analizó transversalmente a una cohorte de pacientes con AR, durante el periodo de octubre a diciembre del año 2022. Para el estudio se registraron variables clínico-epidemiológicas y relacionadas con la vacunación (i.e. acceso a la vacunación, tipo, número de dosis). Se realizó un análisis descriptivo de las variables con el software R-4.3.2. Resultados: Se incluyeron 568 pacientes, 84,1% eran mujeres, con un promedio de edad de 55,5±13,9 años. El 88,7% (504) pacientes, recibieron al menos una dosis de vacuna contra SARS-CoV-2. 85% (483) recibieron dos dosis, mientras que el 60,9% (344) pacientes recibieron el primer refuerzo, y 21,2% el segundo refuerzo. Conclusiones: En esta serie de pacientes paraguayos con AR el porcentaje de vacunación contra SARS-CoV-2 fue más elevado que el registrado en la población general del país. Esto podría estar relacionado con la prioridad de esta población para acceder a las vacunas y a la insistencia de sus médicos en completar el esquema de vacunación.

Introduction: Vaccination in populations exposed to increased risk of severe disease and death consequent to SARS-CoV-2 infection has generated a major impact on global Public Health. Certainly, the benefit has been evidenced mostly in people with chronic comorbidities, where rheumatoid arthritis (RA) plays an important role. Objective: To analyze vaccination against Sars-CoV-2 in paraguayan patients with rheumatoid arthritis (RA) during the COVID19 pandemic. Methods: A multicenter study was carried out, in which a cohort of patients with RA was analyzed cross-sectionally, during the period from October to December 2022. For the study, clinical-epidemiological and vaccination-related variables were recorded (i.e. access to vaccination, type, number of doses). A descriptive analysis of the variables was carried out with the R-4.3.2 software. Results: 568 patients were included, 84.1% were female, with an average age of 55.5±13.9 years. 88.7% (504) patients received at least one dose of SARS-CoV-2 vaccine, 85% (483) received two doses, while 60.9% (344) patients received the first booster, and 21.2% the second booster. Conclusions: In this series of Paraguayan patients with RA the percentage of vaccination against SARS-CoV-2 was higher than that registered in the general population of the country. This could be related to the priority of this population to access vaccines and the insistence of their physicians to complete the vaccination schedule.

Association of class II HLA alleles with susceptibility to develop immune-mediated diseases in Paraguayan patients.

Genetic and nongenetic factors are involved in the pathogenesis of immune-mediated inflammatory diseases (IMIDs). The best-known genetic factor for susceptibility to IMIDs is the human leukocyte antigen (HLA). The aim of the present study was to evaluate the association of HLA class II genes with the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) in the Paraguayan population. We included 254 patients with IMIDs (101 SLE, 103 RA, and 50 SSc) and 50 healthy controls. The haplotypes of five genes corresponding to HLA class II genes and their relationship to the IMIDs studied were determined. Note that 84.6% were women, with a mean age of 43.4 ± 14 years. Among the associated HLA alleles, we found the previously identified risk factors in other populations like HLA-DRB1*03:01 and HLA-DRB1*14:02 for RA, as well as new ones not previously identified, such as DPA1*02:01 for SLE and, DB1*02:01 for RA and SSc. In the genetic association analysis, already known associations have been replicated, and unpublished associations have been identified in Paraguayan patients with IMIDs. This is the first genetic association study in Paraguayan patients with IMIDs.

Palindromic Rheumatism: Just a Pre-rheumatoid Stage or Something Else?

Palindromic rheumatism (PR), a unique clinical entity, has a characteristic clinical presentation with a relapsing/remitting course. It is established that most patients with PR evolve to chronic disease, of which rheumatoid arthritis (RA) is by far the most common. The relationship between PR and RA is unclear, with similarities and differences between the two, and not all patients evolve to RA in the long-term. Therefore, PR is clearly a pre-RA stage for most, but not all, patients. Autoimmunity plays a substantial role in PR, with the same characteristic autoantibody profile observed in RA, although with some differences in the immune response repertoire. Autoinflammation may also be relevant in some cases of PR. Prognostic factors for RA progression are identified but their exact predictive value is not clear. There are several unmet needs in PR, such as the diagnostic criteria and clinical case definition, the pathogenic mechanisms involved in the unusual clinical course, and the evolution to RA, and our understanding of the therapeutic strategy that could best avoid progression to persistent and potentially destructive arthritis.

Anti-carbamylated protein antibody isotype pattern differs between palindromic rheumatism and rheumatoid arthritis.

BACKGROUND: A restricted response against citrullinated peptides/proteins, with less isotype usage, has been found in palindromic rheumatism (PR) in comparison with rheumatoid arthritis (RA). We hypothesized that this different antibody response may be observed for other post-translational modified proteins. We compared the prevalence and isotype usage of two specificities of anti-carbamylated peptide/protein antibodies (Anti-CarP) in patients with PR and RA. METHODS: Cross-sectional study including 54 patients with pure PR and 53 patients with RA, matched by sex, age, disease duration and ACPA. Anti-CarP specificities were determined by home-made enzyme-linked immunosorbent assay tests using a synthetic chimeric fibrin/filaggrin homocitrullinated peptide (CFFHP) and fetal calf serum (FCS) homocitrullinated protein as antigens. IgG, IgA and IgM isotypes were measured. RESULTS: Anti-CarP were positive (CFFHP or FCS) in 24% and 64% of patients with PR and RA, respectively (p < 0.005). All Anti-CarP isotype proportions were significantly lower in PR than in RA: Anti-CarP-IgG (24% versus 51%), Anti-CarP-IgA (7% versus 34%) and Anti-CarP-IgM (7% versus 36%). Mean titers of Anti-CarP isotypes were also lower in PR. In Anti-CarP positive patients, the isotype distribution differed between PR and RA: IgG Anti-CarP was used in all PR patients and in 79% of RA patients. By contrast, a significantly lower isotype usage of both IgA (31% versus 53%) and IgM (31% versus 56%) was observed in PR patients. No significant differences in clinical or demographic characteristics were observed according to Anti-CarP status in PR patients, except for a higher prevalence of ACPA and higher mean titers of ACPA and rheumatoid factor in Anti-CarP positive patients. CONCLUSION: Anti-CarP are found in patients with PR but in a lower proportion and with a different isotype usage from in RA, suggesting a distinct B cell response to homocitrullinated antigens in PR.

Seguridad y supervivencia de las terapias biológicas: primer informe del registro paraguayo-uruguayo de acontecimientos adversos con terapias biológicas Biobadaguay / Safety and survival associated with biologic therapies: first report of the biobadaguay on the Paraguayan-Uruguayan registry of adverse events with biologic therapies

OBJETIVOS: Analizar los acontecimientos adversos (AA) y la supervivencia de las terapias biológicas (TB) en el registro paraguayo-uruguayo de AA, Biobadaguay. MÉTODO: Estudio observacional, prospectivo de duración indeterminada. Se han incluido pacientes al inicio de la TB y controles. Se han registrado variables clínicas, biológicas y relacionadas con el tratamiento. RESULTADOS: Se realizaron 826 registros (650 TB y 176 controles). El 70,9% fueron mujeres y el diagnóstico más frecuente fue la artritis reumatoide (AR) (63,2%). La TB más utilizada fue el adalimumab (56,6%) y la causa más frecuente de interrupción, la ineficacia (42,1%). La incidencia de AA en pacientes con TB fue de 143,9 (128,8-160,8) por 1.000 pacientes/año. En el estudio comparativo de AA en función del diagnóstico, se observó que la artritis idiopática juvenil (AIJ) se asoció a más AA globales (RTI = 2,3; IC 95%: 1,6-3,4; p = 4,27×10−6), mientras que la AR se asoció a un mayor número de AA graves (RTI = 2,20; IC 95%: 1,2-4,1; p = 1,17×10−2). Por otro lado, el tratamiento con tocilizumab se asoció a una mayor tasa de AA (RTI = 2,69; IC 95%: 1,90-3,82; p = 3,13×10−8). El diagnóstico de AIJ, el tratamiento con corticoides y el número de TB previas se asociaron a la disminución de la supervivencia de las TB. CONCLUSIÓN: En este primer informe del registro Biobadaguay, la principal causa de interrupción de la TB fue la ineficacia. Con relación al diagnóstico, la AR y la AIJ se asociaron a un mayor riesgo de AA. En este registro, se identificaron variables relacionadas a una menor supervivencia de las TB

OBJECTIVE: Analyze adverse events (AE) and survival associated with biologic therapies (BT) in the Biobadaguay, the Paraguayan Uruguayan registry of adverse events. METHODS: Prospective, observational study of undetermined duration. Patients on BT at initiation and controls were included. Clinical, biological and treatment variables were registered. RESULTS: A total of 826 registers were entered (650 BT and 176 controls); 70.9% were women and rheumatoid arthritis (RA) was the most frequent diagnosis (63.2%). The BT most often used was adalimumab and the main cause of discontinuation was loss of efficacy (42.1%). The incidence of AE of patients on BT was 143.9 (128.8-160.8) per 1000 patients/year. In the comparative study of AE related to diagnosis, juvenile idiopathic arthrosis (JIA) was associated with a higher overall number of AE (RTI = 2.3; 95%CI: 1.6-3.4; P = 4.27 ×10−6), whereas RA was associated with a higher number of serious AE (RTI = 2.2; 95% CI: 1.2-4.1; P =1.17 ×10−2). On the other hand, treatment with tocilizumab was associated with a higher rate of AE (RTI = 2.69; 95% CI: 1.9-3.82; P = 3.13 ×10−8). In JIA, treatment with corticosteroids and number of previous BT was associated with a decrease in BT survival. CONCLUSION: In this first report of the Biobadaguay registry, the main cause of BT discontinuation was loss of efficacy. In terms of the diagnosis involved, RA and JIA were associated with a higher risk of AE. In this registry, variables related to a shorter survival of BT were identified

Safety and Survival Associated with Biologic Therapies: First Report of the Biobadaguay on the Paraguayan-Uruguayan Registry of Adverse Events with Biologic Therapies. / Seguridad y supervivencia de las terapias biológicas: primer informe del registro paraguayo-uruguayo de acontecimientos adversos con terapias biológicas Biobadaguay.

OBJECTIVE: Analyze adverse events (AE) and survival associated with biologic therapies (BT) in the Biobadaguay, the Paraguayan Uruguayan registry of adverse events. METHODS: Prospective, observational study of undetermined duration. Patients on BT at initiation and controls were included. Clinical, biological and treatment variables were registered. RESULTS: A total of 826 registers were entered (650 BT and 176 controls); 70.9% were women and rheumatoid arthritis (RA) was the most frequent diagnosis (63.2%). The BT most often used was adalimumab and the main cause of discontinuation was loss of efficacy (42.1%). The incidence of AE of patients on BT was 143.9 (128.8-160.8) per 1000 patients/year. In the comparative study of AE related to diagnosis, juvenile idiopathic arthrosis (JIA) was associated with a higher overall number of AE (RTI = 2.3; 95%CI: 1.6-3.4; P = 4.27 ×10-6), whereas RA was associated with a higher number of serious AE (RTI = 2.2; 95% CI: 1.2-4.1; P =1.17 ×10-2). On the other hand, treatment with tocilizumab was associated with a higher rate of AE (RTI = 2.69; 95% CI: 1.9-3.82; P = 3.13 ×10-8). In JIA, treatment with corticosteroids and number of previous BT was associated with a decrease in BT survival. CONCLUSION: In this first report of the Biobadaguay registry, the main cause of BT discontinuation was loss of efficacy. In terms of the diagnosis involved, RA and JIA were associated with a higher risk of AE. In this registry, variables related to a shorter survival of BT were identified.

Calprotectin strongly and independently predicts relapse in rheumatoid arthritis and polyarticular psoriatic arthritis patients treated with tumor necrosis factor inhibitors: a 1-year prospective cohort study.

BACKGROUND: Calprotectin is a biomarker of disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and predicts relapse in juvenile idiopathic arthritis. Higher drug trough serum levels are associated with a good response in patients treated with tumor necrosis factor inhibitors (TNFi). Power Doppler ultrasound synovitis is predictive of relapse and structural damage progression in patients in clinical remission. The purpose of this study was to analyze the accuracy of serum calprotectin levels, drug trough serum levels (TSL), and power Doppler (PD) activity as predictors of relapse in RA and PsA patients in remission or with low disease activity receiving TNFi. METHODS: This was a longitudinal, prospective, 1-year single-center study of 103 patients (47 RA, 56 PsA) receiving TNFi in remission or with low disease activity (28-joint Disease Activity Score (DAS28) ≤ 3.2). The predictive value of serum calprotectin, TNFi TSL, and PD were assessed using receiver operating characteristic (ROC) analyses. To illustrate the predictive performance of calprotectin, TNFi TSL, and PD score, Kaplan-Meier curves were constructed from baseline to relapse. Associations between baseline factors and relapse were determined using Cox regression models. Multivariate models were constructed to analyze the effect of covariates and to fully adjust the association between calprotectin, TNFi TSL, and PD score with relapse. A generalized estimating equation model with an identity link for longitudinal continuous outcomes was used to assess the effect of covariates on TNFi TSL. RESULTS: Ninety-five patients completed 1 year of follow-up, of whom 12 experienced a relapse. At baseline, relapsers had higher calprotectin levels, lower TNFi TSL, and higher PD activity than nonrelapsers. ROC analysis showed calprotectin fully predicted relapse (area under the curve (AUC) = 1.00). TNFi TSL and PD had an AUC of 0.790 (95% confidence interval (CI) 0.691-0.889) and 0.877 (95% CI 0.772-0.981), respectively. Survival analyses and log rank tests showed significant differences between groups according to calprotectin serum levels (p < 0.001), TNFi TSL (p = 0.004), and PD score (p < 0.001). Univariate Cox regression models showed that time-to-remission/low disease activity (hazard ratio (HR) = 1.17, p < 0.001), calprotectin levels (HR = 2.38, p < 0.001), TNFi TSL (HR = 0.47, p = 0.018), and PD score (HR = 1.31, p < 0.001) were significantly associated with disease relapse. In the multivariate analysis, only baseline calprotectin levels independently predicted disease relapse (HR = 2.41, p = 0.002). The generalized estimating equation analysis showed that only disease activity by DAS28-erythrocyte sedimentation rate (ESR) was significantly associated with longitudinal changes in TNFi TSL (regression coefficient 0.26 (0.0676 to 0.0036), p = 0.001). CONCLUSION: Time-to-remission/low disease activity, calprotectin serum levels, TNFi TSL, and PD score were significantly associated with disease relapse. However, only baseline calprotectin serum levels independently predicted disease relapse in RA and PsA patients under TNFi therapy.

Differing specificities and isotypes of anti-citrullinated peptide/protein antibodies in palindromic rheumatism and rheumatoid arthritis.

BACKGROUND: To analyze differences in the recognition of anti-citrullinated peptide/protein antibody (ACPA) citrullinated epitopes and isotypes in patients with palindromic rheumatism (PR) and rheumatoid arthritis (RA). METHODS: ACPA fine specificities (citrullinated peptides of enolase, fibrin, and vimentin) and isotypes (IgG, IgM, and IgA) were analyzed in 54 patients with longstanding PR and 54 patients with established RA. RESULTS: CCP2 tested positive in 66.7% of patients with PR and RA. The ACPA distribution of fine specificities and isotypes differed between PR and RA patients. PR patients had a lower frequency of fine ACPA specificities than RA patients, which was significant in the case of a peptide derived from vimentin (PR 24.1% vs. 59.3% RA; p < 0.001). The mean number of ACPA specificities was lower in PR than in RA patients, and only 25.9% of PR patients recognized ≥2 additional specificities compared with 46.3% of RA patients. Significantly less isotype usage, especially IgA, was observed in PR patients. CONCLUSION: The ACPA immune response differed in patients with PR and RA, with fewer fine specificities and isotype usage in patients with PR. Some patients with PR may have impaired maturation of the B-cell response against citrullinated peptides with no progression to RA.

Calprotectin and TNF trough serum levels identify power Doppler ultrasound synovitis in rheumatoid arthritis and psoriatic arthritis patients in remission or with low disease activity.

BACKGROUND: Serum levels of calprotectin, a major S100 leucocyte protein, are associated with disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. Higher drug trough serum levels are associated with good response in patients treated with tumour necrosis factor inhibitors (TNFi). Power Doppler ultrasound (PDUS) synovitis is predictive of flare and progression of structural damage in patients in clinical remission. The purpose of this study was to analyse the accuracy of calprotectin and TNFi trough serum levels in detecting PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity who were receiving TNFi. METHODS: We conducted a cross-sectional study of 92 patients (42 with RA, 50 with PsA) receiving adalimumab (ADA), etanercept (ETN) or infliximab who were in remission or had low disease activity (28-joint Disease Activity Score based on erythrocyte sedimentation rate <3.2). Associations of calprotectin, TNFi trough serum levels and acute phase reactants with PDUS synovitis were assessed using correlation and linear regression analyses. The accuracy and discriminatory capacity in detecting PDUS synovitis was assessed using ROC curves. RESULTS: PDUS synovitis was found in 62.4 % of RA patients and 32 % of PsA patients. Both RA and PsA patients with PDUS synovitis had higher calprotectin levels and lower TNFi trough serum levels. Calprotectin positively correlated with ultrasound scores (all r coefficients >0.50 in RA). Calprotectin correlated with the PDUS synovitis score in patients treated with ADA and ETN. Using PDUS synovitis (yes or no) as the reference variable, calprotectin had an AUC of 0.826. The best cut-off was ≥1.66 µg/ml, with a likelihood ratio of 2.77. C-reactive protein (AUC 0.673) and erythrocyte sedimentation rate (AUC 0.731) had a lower discriminatory capacity. TNFi trough serum levels were significantly associated with PDUS synovitis (OR 0.67, 95 % CI 0.52-0.85, p < 0.001) but their accuracy (AUC <0.5) was less than that of calprotectin. TNFi trough serum levels were inversely correlated with calprotectin and PDUS synovitis in RA and PsA patients receiving ADA and ETN. CONCLUSIONS: Calprotectin and TNFi trough serum levels may help identify PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity.

Serum Calprotectin Versus Acute-Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors.

OBJECTIVE: To compare the accuracy of serum calprotectin and acute-phase reactants (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) in stratifying disease activity in rheumatoid arthritis (RA) patients receiving tumor necrosis factor inhibitors (TNFi), and to correlate calprotectin levels with TNFi trough serum levels. METHODS: We conducted a cross-sectional study of 87 RA patients receiving adalimumab, etanercept (ETN), or infliximab (IFX); 56 psoriatic arthritis (PsA) patients and 40 healthy blood donors were included as controls. Associations between calprotectin, CRP, and ESR and composite articular indices (Disease Activity Score in 28 joints [DAS28], Simplified Disease Activity Index [SDAI], and Clinical Disease Activity Index) were analyzed by correlation and linear regression and the accuracy and discriminatory capacity of calprotectin by receiver operator characteristic curves (area under the curve [AUC]). RESULTS: Calprotectin levels correlated better with all composite activity indices than CRP and ESR (all r coefficients >0.70). Calprotectin levels were significantly lower in RA and PsA patients in clinical remission compared with those with low disease activity for all articular indices. In RA, ESR discriminated between remission and low disease activity only when using DAS28, and CRP only with SDAI. In RA patients in remission/low disease activity, calprotectin but not CRP or ESR distinguished between patients with no swollen joints and those with ≥1 swollen joint (1.74 µg/ml versus 3.04 µg/ml; P = 0.010). Using DAS28 ≥2.6 as the reference variable, calprotectin showed an AUC of 0.92; the best cutoff was ≥2.47 µg/ml with a likelihood ratio of 6.3 (95% confidence interval 2.5-15.8). Calprotectin serum levels inversely correlated with trough serum drug levels of ETN (ρ = -0.671, P < 0.001) and IFX (ρ = -0.729, P = 0.017). CONCLUSION: Calprotectin may more accurately discriminate disease activity in RA patients receiving TNFi than acute-phase reactants, even in patients with low inflammatory activity.

Calprotectin more accurately discriminates the disease status of rheumatoid arthritis patients receiving tocilizumab than acute phase reactants.

OBJECTIVE: To compare the accuracy of serum calprotectin levels, CRP and ESR in stratifying disease activity in RA patients receiving tocilizumab (TCZ). METHODS: Cross-sectional study of 33 RA patients receiving TCZ. DAS28, Simplified Disease Activity Index, Clinical Disease Activity Index, joint counts and serum levels of CRP, ESR, calprotectin and TCZ were measured. Associations between calprotectin, ESR and CRP and articular indices were analysed by correlation and linear regression. The accuracy and discriminatory capacity of calprotectin was assessed by receiver operating characteristic curves (area under the curve). RESULTS: Calprotectin levels, but not CRP or ESR, were strongly correlated with all composite indices (all r coefficients over 0.50). Calprotectin, but not CRP or ESR, was significantly lower in patients in remission compared with those with low disease activity [1.57 µg/ml (s.d. 1) vs 3.35 µg/ml (s.d. 1), P = 0.001]. In a fully adjusted model (R(2) = 0.82), DAS28-ESR increased 0.48 units per µg/ml calprotectin increase (P < 0.001). Using a DAS28 >3.2 as the reference variable, calprotectin showed an area under the curve of 0.922, and the best cut-off was 5.19 µg/ml (odds ratio 11.5). CRP levels, but not calprotectin, were dependent on detectable TCZ trough serum levels. CONCLUSION: Calprotectin serum levels seem to be an accurate biomarker for assessing disease activity in RA patients receiving TCZ.

Is there subclinical synovitis in patients with palindromic rheumatism in the intercritical period? a clinical and ultrasonographic study according to anticitrullinated protein antibody status.

OBJECTIVE: To investigate the presence of subclinical synovitis by ultrasound (US) and the clinical phenotype in patients with palindromic rheumatism (PR) according to anticitrullinated protein antibody (ACPA) status. METHODS: Fifty-four patients with PR were studied. Clinical, demographic, serological, and therapeutic characteristics were compared in ACPA-positive and ACPA-negative patients. US searching for synovial hypertrophy (SH) and power Doppler signal (PDUS) in 22 joints of the hands was performed in the intercritical period. The results were compared according to ACPA status and with a healthy control group (n = 30). In 10 patients, US was performed during the joint attack. RESULTS: Most patients were female (63%) with a mean disease duration of 11.6 ± 10.7 years. Thirty-six patients (66.7%) were ACPA-positive. ACPA-positive patients had a shorter duration of attacks, a younger age, and less knee involvement at disease onset. US examination showed SH grade ≥ 1 in 79.6% of patients with PR and 50% of controls. Significant US results (SH ≥ 2 or PDUS) were observed in 2.7% and 1.4% of joints assessed and in 33% and 25.9% of patients with PR, respectively. Only 4 patients (7.4%) had US active synovitis (SH ≥ 2 plus PDUS) in at least 1 joint. US assessment showed no significant differences between ACPA-positive and ACPA-negative patients. PDUS was observed in 7 out of 10 patients during attacks. CONCLUSION: Some differences emerged in the clinical phenotype of PR according to ACPA status. Most patients with PR do not have US subclinical synovitis in the intercritical period, even those who are ACPA-positive.

Reducción de dosis de terapias biológicas en enfermedades reumáticas: análisis descriptivo de 153 pacientes en condiciones de práctica clínica / Reduction of biological agent dose in rheumatic diseases: descriptive analysis of 153 patients in clinical practice conditions

Objetivo. Analizar la frecuencia y características de la reducción de dosis de fármacos biológicos en una cohorte de pacientes con artritis crónica, en condiciones de práctica clínica de un hospital de tercer nivel. Material y métodos. Estudio descriptivo y transversal, que incluyó a todos los pacientes visitados consecutivamente durante 6 meses(junio de 2011-noviembre de 2011) por un solo investigador, con pacientes que habían recibido al menos una dosis de fármaco biológico durante el año 2011. Resultados. Se incluyeron 153 pacientes: artritis reumatoide (AR) (n = 82), espondilitis anquilosante (n = 29), artritis psoriásica (n = 20)y grupo miscelánea (n = 22) con una evolución media de 14,9 ± 7,7 años. En el momento del análisis, 70 pacientes (45,7%) estaba con dosis reducida (un 50% en el grupo miscelánea; un 50% en artritis psoriásica; un 48,2% en espondilitis anquilosante, y un 42,6% en AR). El tiempo medio de reducción de dosis fue de 17,4 ± 17,5 meses. Los fármacos biológicos más utilizados a dosis reducidas fueron: etanercept, adalimumab y tocilizumab; el 57,6, el 54,9 y el 40 respectivamente de los pacientes tratados con estos agentes lo hacían a dosis reducidas. Los pacientes con dosis reducidas en comparación con aquellos con dosis normales tenían un mismo tiempo de evolución de la enfermedad, pero recibían menos FAME, glucocorticoides y AINE, con un tiempo similar de uso del agente biológico. Los pacientes con AR y dosis reducidas tenían, en el momento del análisis, mayores índices de remisión que los pacientes con dosis normales (82,9 vs. 34%, p < 0,0001). La decisión terapéutica en el momento del análisis fue mantener la dosis reducida en la práctica totalidad de los pacientes. Conclusión. En nuestra práctica clínica, el 45,7% de los pacientes con artritis crónica reciben terapia biológica a dosis reducidas, tras haber alcanzado la remisión o baja actividad a dosis estándares, manteniendo la mayoría de ellos un buen control de la enfermedad (AU)

Objective: To analyze the frequency and characteristics of dose reduction of biological agents in a cohort of patients with chronic arthritis, in clinical practice conditions in a tertiary level hospital. Material and methods: Descriptive, cross-sectional study, which included all patients, followed consecutively during 6 months (June 2011-November 2011), by one investigator, with patients who at least have received one dose of biological agents in 2011. Results: We included 153 patients: Rheumatoid arthritis (RA) (n = 82), ankylosing spondylitis (n = 29), psoriatic arthritis (n = 20), and miscellaneous group (n = 22). Mean disease duration was 14.9 ± 7.7 years. At the time of analysis, 70 patients (45.7%) were receiving low doses of biological therapy (50% in miscellaneous group group, 50% in psoriatic arthritis, 48.2% in ankylosing spondylitis, and 42.6% in RA). Mean time of dosage reduction was 17.4 ± 17.5 months. The most common biological agents used in low dose were: etanercept, adalimumab and tocilizumab; 57.6%, 54.9% and 40% respectively, in patients with a reduced dose of biological therapy. The patients at low dose of biological therapy compared with standard dose, had similar mean disease duration, but received significantly less DMARDs, glucocorticoids and NSAIDs, and similar biological agent duration. RA patients with reduced biological treatment, at the time of analysis, had higher remission rates versus patients receiving a standard dose (82.9% vs 34%, p < 0.0001). The medical decision at the time of analysis was to maintain low-dosage biological treatment in almost all patients. Conclusion: In our clinical practice, 45.7% of our chronic arthritis patients receive low dose of biological therapy, after achieving remission or low activity at standard doses, maintaining a good control of the disease (AU)

Reduction of biological agent dose in rheumatic diseases: descriptive analysis of 153 patients in clinical practice conditions.

OBJECTIVE: To analyze the frequency and characteristics of dose reduction of biological agents in a cohort of patients with chronic arthritis, in clinical practice conditions in a tertiary level hospital. MATERIAL AND METHODS: Descriptive, cross-sectional study, which included all patients, followed consecutively during 6 months (June 2011-November 2011), by one investigator, with patients who at least have received one dose of biological agents in 2011. RESULTS: We included 153 patients: Rheumatoid arthritis (RA) (n=82), ankylosing spondylitis (n=29), psoriatic arthritis (n=20), and miscellaneous group (n=22). Mean disease duration was 14.9±7.7 years. At the time of analysis, 70 patients (45.7%) were receiving low doses of biological therapy (50% in miscellaneous group group, 50% in psoriatic arthritis, 48.2% in ankylosing spondylitis, and 42.6% in RA). Mean time of dosage reduction was 17.4±17.5 months. The most common biological agents used in low dose were: etanercept, adalimumab and tocilizumab; 57.6%, 54.9% and 40% respectively, in patients with a reduced dose of biological therapy. The patients at low dose of biological therapy compared with standard dose, had similar mean disease duration, but received significantly less DMARDs, glucocorticoids and NSAIDs, and similar biological agent duration. RA patients with reduced biological treatment, at the time of analysis, had higher remission rates versus patients receiving a standard dose (82.9% vs 34%, p<0.0001). The medical decision at the time of analysis was to maintain low-dosage biological treatment in almost all patients. CONCLUSION: In our clinical practice, 45.7% of our chronic arthritis patients receive low dose of biological therapy, after achieving remission or low activity at standard doses, maintaining a good control of the disease.

The Spanish version of the Fibromyalgia Rapid Screening Tool: translation, validity and reliability.

OBJECTIVE: Despite showing acceptable psychometric properties, the criterion validity of the original Fibromyalgia Rapid Screening Tool (FiRST) has been called into question for including insufficiently challenging comparison groups. Consequently our objective was to validate a Spanish version of the FiRST including pain disorders more analogous to fibromyalgia. METHODS: The FiRST was translated following international standards. Internal consistency and temporal stability were assessed. The ability of the FiRST global score as a screening tool for fibromyalgia (criterion validity) was assessed by logistic regression analysis. To determine the degree to which potential confounders might affect the criterion validity of the FiRST (divergent validity), it was reassessed by hierarchical multivariate logistic regression, entering demographics in a first step, followed by pain, anxiety and depression, catastrophizing, disability and the FiRST global score in a last step. RESULTS: The final sample comprised 257 patients (67% cases of fibromyalgia). The Spanish version of the FiRST showed acceptable internal consistency, reliability and criterion validity. The FiRST was able to discriminate between fibromyalgia and non-fibromyalgia patients even after controlling for the effect of potential confounders. However, both criterion and divergent validity were challenged by a moderate specificity. CONCLUSION: The Spanish version of the FiRST may be used as a screening tool for fibromyalgia even in those patients whose cognitive style is characterized by catastrophizing about pain and high levels of functional disability, anxiety and depression. The clinical consequences of the moderate specificity shown by this Spanish version of the FiRST are discussed.

Palindromic rheumatism with positive anticitrullinated peptide/protein antibodies is not synonymous with rheumatoid arthritis. A longterm followup study.

OBJECTIVE: To analyze longterm progression to rheumatoid arthritis (RA) and the predictive value of anticitrullinated peptide/protein antibodies (ACPA) in palindromic rheumatism (PR). METHODS: We selected all patients in our clinic with PR who had at least 1 ACPA measurement. We included only patients with pure PR, defined as no evidence of associated rheumatic disease at the first serum ACPA measurement. Clinical characteristics, serum ACPA levels, duration of PR until serum ACPA measurement, and total followup time were recorded. The outcome variable was the definitive diagnosis of RA. The prognostic value of ACPA status in pure PR for a definite diagnosis of RA was analyzed by different statistical methods. RESULTS: Seventy-one patients (54 women/17 men) with a PR diagnosis were included. Serum ACPA were positive in 52.1%. After a mean followup of 7.6 ± 4.7 years since the first ACPA measurement, 24 patients (33.8%) progressed to chronic disease: 22% RA, 5.6% systemic lupus erythematosus, and 5.6% other diseases. The positive likelihood ratio of ACPA status for RA was 1.45, and the area under the receiver-operating characteristic curve of ACPA titers was 0.60 (95% CI 0.45-0.75). Progression to RA was more frequently seen in ACPA-positive than in ACPA-negative patients (29.7% vs 14.7%), but the difference was not significant (hazard ratio 2.46, 95% CI 0.77-7.86). Mean ACPA levels of patients with pure PR did not differ significantly from those of patients who progressed to RA. CONCLUSION: ACPA are frequently found in the sera of patients with PR, and a significant proportion of these patients do not progress to RA in the long term.

[How does one manage patients with rheumatoid arthritis and positive serology to hepatitis B, hepatitis C, human immunodeficiency virus?]. / ¿Cómo manejar al paciente con artritis reumatoide y serología virus de hepatitis B, hepatitis C, virus de la inmunodeficiencia humana?

Chronic viral infections in rheumatic patients are a diagnostic and therapeutic challenge. Some of the disease-modifying antirheumatic drugs (DMARD) commonly used in rheumatoid arthritis, such as methotrexate and leflunomide, are hepatotoxic. With biological therapy, which is now widely used in patients refractory to these and other DMARD, some cases of reactivation of hepatitis B, even fulminant cases, have been reported, especially when employing TNF antagonists and rituximab, so their use must be carefully assessed and usually accompanied by antiviral therapy. However, there have not been reports of reactivation of hepatitis C after immunosuppressive therapy. In patients with HIV infection, administration of immunosuppressive therapy carries a high risk of opportunistic infections, although the new highly active antiviral therapy allows the use of some drugs in selected cases.

¿Cómo manejar al paciente con artritis reumatoide y serología virus de hepatitis B, hepatitis C, virus de la inmunodeficiencia humana? / How does one manage patients with rheumatoid arthritis and positive serology to hepatitis B, hepatitis C, human immunodeficiency virus?

Las infecciones virales crónicas en un paciente reumático constituyen un reto diagnóstico y terapéutico. Algunos de los fármacos antirreumáticos modificadores de la enfermedad (FAME) más utilizados en la artritis reumatoide, como el metotrexato y la leflunomida, presentan riesgo de hepatotoxicidad. Con la terapia biológica, que es hoy en día ampliamente utilizada en pacientes refractarios a estos y otros FAME, se han descrito casos de reactivación de hepatitis B, incluso fulminante, especialmente con los antagonistas del TNF y rituximab, por lo que su utilización ha de ser cuidadosamente valorada y, generalmente, administrada junto con tratamiento antiviral. Sin embargo, no se han descrito casos de reactivación de hepatitis C tras terapia inmunosupresora. En los pacientes con serología VIH la administración de tratamiento inmunosupresor conlleva un elevado riesgo de infecciones oportunistas, aunque la nueva terapia antiviral altamente activa permite utilizar algunos fármacos en casos seleccionados (AU)

Chronic viral infections in rheumatic patients are a diagnostic and therapeutic challenge. Some of the disease-modifying antirheumatic drugs (DMARD) commonly used in rheumatoid arthritis, such as methotrexate and leflunomide, are hepatotoxic. With biological therapy, which is now widely used in patients refractory to these and other DMARD, some cases of reactivation of hepatitis B, even fulminant cases, have been reported, especially when employing TNF antagonists and rituximab, so their use must be carefully assessed and usually accompanied by antiviral therapy. However, there have not been reports of reactivation of hepatitis C after immunosuppressive therapy. In patients with HIV infection, administration of immunosuppressive therapy carries a high risk of opportunistic infections, although the new highly active antiviral therapy allows the use of some drugs in selected cases (AU)