Management of Peripheral Arthritis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations. METHODS: A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings. RESULTS: The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain. CONCLUSION: Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations.

Complementary Therapies and Their Association with Problems in Therapeutic Adherence to Conventional Synthetic DMARDs in Rheumatoid Arthritis: A Cross-Sectional Study.

The use of complementary therapies is highly prevalent among patients with rheumatoid arthritis (RA). Nevertheless, the use of complementary medicine could involve problems in the following of scientifically accepted treatments. To date, there is limited information regarding the association of nonconventional therapies with problems regarding compliance with the treatment. Therefore, the objective of this study was to identify whether the utilization of complementary therapies is associated with a high risk of problems regarding therapeutic adherence to conventional synthetic disease-modifying anti-rheumatic drugs (cs-DMARDs) in RA patients. A survey was performed with RA patients in an outpatient rheumatology clinic in a university hospital; the use of complementary therapies, as well as their type, was identified. To assess problems with therapeutic adherence, we used the four-item Morisky-Green scale. A comprehensive assessment of clinical and therapeutic characteristics was performed. Univariable and multivariable models were performed to identify the risk of problems with therapeutic adherence in users of complementary therapies. In total, 250 RA patients were included; 92% used complementary therapies. Of them, the most frequently used were herbal medicine (65%), homeopathy (64%), and cannabis and its derivatives (51%). In the univariable logistic regression analysis, the factors associated with problems in the therapeutic adherence to cs-DMARDs were age (p = 0.019), the presence of other comorbidities (p = 0.047), and the use of complementary therapies (p = 0.042). After controlling for potential confounders, the use of complementary therapies increased the risk of problems with therapeutic adherence to cs-DMARDs (adjusted OR = 2.84, 95% CI = 1.06-7.63, p = 0.037). We concluded that the use of complementary therapies increases the risk of problems with therapeutic adherence. Therefore, for physicians and healthcare professionals, the early identification of the use of nonconventional therapies in their RA patients is required, followed by a directed discussion with their patients about the risks and benefits to which they could be exposed to complementary therapies.

Hiperuricemia asintomática y enfermedad arterial coronaria / Asymptomatic hyperuricaemia and coronary artery disease

Antecedentes: El ácido úrico se ha relacionado con la tendencia de precipitarse para formar cristales, que se presenta desde manera asintomática hasta con artritis, tofos o litiasis renal. Con anterioridad, se ha asociado la hiperuricemia asintomática a la presencia de enfermedad cardiovascular. Objetivos: Determinar la asociación de enfermedad arterial coronaria compleja en pacientes con hiperuricemia asintomática. Material y métodos: Se realizó estudio observacional, transversal, retrospectivo, unicéntrico. En un hospital de tercer nivel de México, en el periodo comprendido de junio del 2017 a marzo del 2019. Se incluyó a todos los pacientes que ingresaron para realizar angiografía coronaria; se excluyó a los pacientes con gota, uso de diuréticos y enfermedad renal crónica. Resultados: Durante el periodo del estudio se seleccionó a un total de 300 pacientes, de los cuales 40% presentaron hiperuricemia. Los pacientes con hiperuricemia eran de mayor edad (59 vs. 63; p = 0,002). El grupo de pacientes con hiperuricemia asintomática tuvo mayor proporción de lesiones coronarias complejas (64 vs. 35%; p ≤ 0,0001), así como también mayor puntuación del SYNTAX I score (27 vs. 17; p ≤ 0,001). Hubo mayor probabilidad de presentar lesiones coronarias complejas en este grupo de pacientes (OR 3,4; p ≤ 0,0001). Además, en la división por grupos de nivel de ácido úrico, se relacionaba con la presencia de lesiones coronarias complejas (Q1 = 0,5; p = 0,06); (Q2 = 2; p = 0,01) y (Q3 = 3; p ≤ 0,0001). Conclusión: Los pacientes con hiperuricemia asintomática tienen mayor riesgo de presentar lesiones coronarias complejas.(AU)

Background: Uric acid has been related to a tendency to precipitate to form crystals, presenting asymptomatically, until the formation of arthritis, tophi or renal lithiasis. Previously, the presence of asymptomatic hyperuricaemia has been associated with the presence of cardiovascular disease. Objectives: To determine the association of complex coronary artery disease in patients with asymptomatic hyperuricaemia. Material and methods: An observational retrospective, transversal, unicentric study was conducted in a tertiary hospital in Mexico, in the period from June 2017 to March 2019. All patients admitted for coronary angiography were included; patients with gout, use of diuretics and chronic kidney disease were excluded. Results: During the study period, a total of 300 patients were collected, of which 40% presented hyperuricaemia. The patients with hyperuricaemia were older (59 vs. 63, P = .002). The group of patients with asymptomatic hyperuricaemia had a higher proportion of complex coronary lesions (64 vs. 35%, P ≤ .0001) as well as a higher SYNTAX I score (27 vs. 17, P ≤ .001). There was a higher probability of presenting complex coronary lesions in this group of patients (OR 3.4, P ≤ .0001). In addition, in the group division of uric acid levels, it was related to the presence of complex coronary lesions (Q1 = .5, P = .06), (Q2 = 2, P = .01) and (Q3 = 3, P ≤ .0001). Conclusion: Asymptomatic hyperuricaemia has a higher prevalence and association of presenting complex coronary lesions.(AU)

Actualización de las guías del tratamiento farmacológico de la artritis reumatoide del Colegio Mexicano de Reumatología 2018 / Update of the Mexican College of Rheumatology Guidelines for the Pharmacological Treatment of Rheumatoid Arthritis, 2018

Los avances terapéuticos en la artritis reumatoide obligan a revisión periódica de las guías de tratamiento. Objetivo: Actualizar las guías del Colegio Mexicano de Reumatología del tratamiento farmacológico de la artritis reumatoide. Método: Participaron reumatólogos certificados de diferentes instituciones de salud y regiones del país. Se conformaron equipos de trabajo que revisaron las guías previas, elaboraron nuevas preguntas, revisaron la literatura y calificaron la evidencia, que fue presentada y discutida en sesión plenaria. Las conclusiones se comentaron con infectólogos, ginecobstetras y pacientes. Se emiten recomendaciones basadas en niveles de evidencia de acuerdo con la metodología GRADE. Resultados: Se presentan recomendaciones actualizadas para el empleo de los medicamentos disponibles en México hasta 2017 para el tratamiento de la artritis reumatoide. Se enfatiza la importancia del control adecuado y sostenido de la enfermedad y se describen aspectos relevantes de seguridad. Se incluyen conflictos bioéticos y se invita a la acción gubernamental para fortalecer el tratamiento adecuado de la enfermedad. Conclusiones: La actualización de las recomendaciones del Colegio Mexicano de Reumatología del tratamiento farmacológico de la artritis reumatoide integra la mejor información disponible para ser utilizada en el sistema de salud de México.(AU)

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 emphasized 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.(AU)

Psoriatic arthritis in patients with psoriasis: A clinical-epidemiological study at a dermatology center in western Mexico.

BACKGROUND/OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory illness. Approximately, 15% of psoriasis patients have undiagnosed PsA. In Mexico, we found no related studies. Our objective was to investigate the clinical-epidemiological characteristics of PsA in psoriasis patients in western Mexico. METHODS: A cross-sectional study including Mexican patients with clinical and histopathological diagnosis of psoriasis. Physical examination, rheumatoid factor analysis and radiographies of axial and peripheral skeleton were performed. The prevalence of PsA using the CASPAR criteria, age, sex; clinical variants of PsA, psoriasis type and the Psoriasis Area and Severity Index (PASI), were assessed. Descriptive and inferential statistics were used. RESULTS: Of 90 patients with psoriasis, 48 met the criteria for PsA, with a prevalence of 53%, and average age of 50 ± 15 years. Predominating were, the female sex in 29 (60%), the axial variant of PsA in 24 (50%), and psoriasis plaques in 40 (83%). The average PASI was 12 ± 11. All cases were rheumatoid factor negative. These variables were not significantly different when comparing subjects with and without PsA, except for the female sex (60% vs. 7%; P < 0.001). CONCLUSIONS: Patients with psoriasis should intentionally be evaluated jointly Dermatologists and Rheumatologists searching joint involvement given the high prevalence of PsA previously undiagnosed.

Deformación miocárdica de la aurícula izquierda en pacientes con lupus eritematoso sistémico / Left Atrial Strain in Patients With Systemic Lupus Erythematosus

Antecedentes: En los pacientes con lupus eritematoso sistémico (LES) la disfunción diastólica del ventrículo izquierdo (DDVI) puede ser la única manifestación de involucro cardiaco anticipando una disfunción sistólica. Se ha visto que la deformación miocárdica de la aurícula izquierda (AI), mediante el strain longitudinal global de la AI (SLGAI), puede llegar a ser de utilidad en valorar la función diastólica. Objetivo: Evaluar la función de la AI mediante la deformación miocárdica en pacientes con LES. Comparar el strain de la AI en pacientes con LES activos, inactivos y controles. Métodos: Se incluyeron 50 pacientes con LES y se compararon con controles sanos pareados por edad y sexo. Se midió por ecocardiograma transtorácico la deformación miocárdica mediante el SLGAI, el strain de las 3 fases del ciclo de la AI y la tasa de strain. La diferencia entre los grupos se analizó de forma univariante. Resultados: El SLGAI en pacientes con LES fue menor que en los controles sanos (41,6% vs. 50,5%; p=0,02), así como también fue menor en las 3 fases del ciclo de la AI. No hubo diferencias en la tasa de strain en ambos grupos (LES 2,5s−1 vs. controles sanos 2,75s−1; p=0,1). También se encontró que el SLGAI fue menor en pacientes activos en comparación con controles e inactivos. Conclusiones: Los pacientes con LES tienen menor deformación miocárdica de la AI, lo que se expresa como una menor función diastólica correlacionando con daño miocárdico subclínico precoz.(AU)

Background: In patients with systemic lupus erythematosus (SLE), left ventricle diastolic dysfunction (LVDD) may be the only manifestation of cardiac involvement in anticipation of systolic dysfunction. It has been seen that myocardial deformation of the left atrium (LA), through the LA global longitudinal strain (LAGLS), may be useful in assessing diastolic function. Objective: To evaluate LA function through myocardial deformation in patients with LES, and compare the LA strain in patients with active, inactive and controls. Methods: Fifty patients with SLE were included and compared with 50 healthy controls paired by age and gender. Myocardial deformation was measured by transthoracic echocardiogram, to investigate the LAGLS, the strain of the three phases of the LA cycle and the strain rate. The differences between groups were compared in univariate analysis. Results: LAGLS in SLE patients was less than in the controls (41.6% vs. 50.5%; p=.02), and in the 3 phases of the LA cycle. There were no differences in the LA strain rate in both groups (SLE 2.5s−1 vs. controls 2.75s−1; p=.1). It was also found that the LAGLS was lesser in active patients than controls and inactive. Conclusions: SLE patients have lower myocardial deformation of the LA, which is expressed as a lower diastolic function correlating with early subclinical myocardial damage.(AU)

Left Atrial Strain in Patients With Systemic Lupus Erythematosus. / Deformación miocárdica de la aurícula izquierda en pacientes con lupus eritematoso sistémico.

BACKGROUND: In patients with systemic lupus erythematosus (SLE), left ventricle diastolic dysfunction (LVDD) may be the only manifestation of cardiac involvement in anticipation of systolic dysfunction. It has been seen that myocardial deformation of the left atrium (LA), through the LA global longitudinal strain (LAGLS), may be useful in assessing diastolic function. OBJECTIVE: To evaluate LA function through myocardial deformation in patients with LES, and compare the LA strain in patients with active, inactive and controls. METHODS: Fifty patients with SLE were included and compared with 50 healthy controls paired by age and gender. Myocardial deformation was measured by transthoracic echocardiogram, to investigate the LAGLS, the strain of the three phases of the LA cycle and the strain rate. The differences between groups were compared in univariate analysis. RESULTS: LAGLS in SLE patients was less than in the controls (41.6% vs. 50.5%; p=.02), and in the 3 phases of the LA cycle. There were no differences in the LA strain rate in both groups (SLE 2.5s-1 vs. controls 2.75s-1; p=.1). It was also found that the LAGLS was lesser in active patients than controls and inactive. CONCLUSIONS: SLE patients have lower myocardial deformation of the LA, which is expressed as a lower diastolic function correlating with early subclinical myocardial damage.

Asymptomatic hyperuricaemia and coronary artery disease. / Hiperuricemia asintomática y enfermedad arterial coronaria.

BACKGROUND: Uric acid has been related to a tendency to precipitate to form crystals, presenting asymptomatically, until the formation of arthritis, tophi or renal lithiasis. Previously, the presence of asymptomatic hyperuricaemia has been associated with the presence of cardiovascular disease. OBJECTIVES: To determine the association of complex coronary artery disease in patients with asymptomatic hyperuricaemia. MATERIAL AND METHODS: An observational retrospective, transversal, unicentric study was conducted in a tertiary hospital in Mexico, in the period from June 2017 to March 2019. All patients admitted for coronary angiography were included; patients with gout, use of diuretics and chronic kidney disease were excluded. RESULTS: During the study period, a total of 300 patients were collected, of which 40% presented hyperuricaemia. The patients with hyperuricaemia were older (59 vs. 63, P = .002). The group of patients with asymptomatic hyperuricaemia had a higher proportion of complex coronary lesions (64 vs. 35%, P ≤ .0001) as well as a higher SYNTAX I score (27 vs. 17, P ≤ .001). There was a higher probability of presenting complex coronary lesions in this group of patients (OR 3.4, P ≤ .0001). In addition, in the group division of uric acid levels, it was related to the presence of complex coronary lesions (Q1 = .5, P = .06), (Q2 = 2, P = .01) and (Q3 = 3, P ≤ .0001). CONCLUSION: Asymptomatic hyperuricaemia has a higher prevalence and association of presenting complex coronary lesions.

Update of the Mexican College of Rheumatology Guidelines for the Pharmacological Treatment of Rheumatoid Arthritis, 2018. / Actualización de las guías del tratamiento farmacológico de la artritis reumatoide del Colegio Mexicano de Reumatología 2018.

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 emphasized 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.

Expression patterns of CD28 and CTLA-4 in early, chronic, and untreated rheumatoid arthritis.

BACKGROUND: T-cell activation pathways have been proposed as trigger mechanisms in the pathogenesis of rheumatoid arthritis (RA). CD28 and CTLA-4 play major roles in regulating the stimulatory and inhibitory co-signals in T cells. OBJECTIVE: To analyze the association between soluble and surface expression of CD28 and CTLA-4 with the clinical parameters of RA patients. METHODS: A total of 35 RA patients classified as early RA (n = 14), chronic RA (n = 14), and untreated RA (n = 7), as well as 7 age- and sex-matched control subjects (CS) were included. Surface expression of CD28 and CTLA-4 on T cells was evaluated by flow cytometry. Soluble levels of CD28 (sCD28), CTLA-4 (sCTLA-4), and anti-CCP antibodies were measured by ELISA. RESULTS: A significant lower percentage of CD8 + T cells positive to CD28 (CS = 64.9% vs RA = 42.7%, P = .04), and diminished surface expression of CD28 (CS: MFI = 122.9 vs RA: MFI = 33.1, P = .006), were found in chronic RA patients compared to CS. Higher sCD28 were observed in early RA patients compared with chronic RA patients (P < .05). sCTLA-4 was found increased in untreated RA patients compared to early RA patients (P < .05). sCD28 concentration correlated with anti-CCP levels (rho = -0.12; P = .032). The soluble and surface expressions of CTLA-4 were not associated with RA clinical parameters. CONCLUSIONS: In RA, the percentage of CD8 + CD28+ T cells decreases and expresses fewer membrane CD28 than CS. sCD28 levels are lower in chronic RA and are associated negatively with anti-CCP levels. sCTLA 4 levels are lower in early RA patients than in untreated RA patients.

Two-Year Safety and Effectiveness of Peficitinib in Moderate-To-Severe Rheumatoid Arthritis: A Phase IIb, Open-Label Extension Study.

INTRODUCTION: Peficitinib is a novel orally bioavailable, once-daily Janus kinase (JAK) inhibitor approved in Japan for the treatment of rheumatoid arthritis (RA). This 2-year extension study of two global phase IIb trials investigated the long-term safety and effectiveness of peficitinib. METHODS: All eligible patients with moderate-to-severe RA including patients in the placebo group who participated in one of two global phase IIb trials ('with methotrexate' or 'without methotrexate') were included in this 2-year open-label extension study and were converted to peficitinib 100 mg once daily. The primary objective was to evaluate an additional 2 years of safety by assessing treatment-emergent adverse events (AEs) and clinical laboratory evaluations for 105 weeks. Evaluation of an additional 2 years of effectiveness using American College of Rheumatology (ACR) 20/50/70 responses was the exploratory objective. RESULTS: Overall, 611 patients were enrolled in the extension study: 319 (52.2%) patients completed the study and 292 (48%) discontinued treatment, including for withdrawal of patient consent (n = 96), failure to achieve low disease activity (n = 62), and AE not including death (n = 41). AEs were reported in 463 (76%) patients. The most common AEs (per 100 patient-years) were upper respiratory tract infections (9.9) and urinary tract infections (7.2). Serious AEs were reported in 80 (13%) patients, with incidences per 100 patient-years of serious infections 2.7, herpes zoster 1.5 (including one herpes zoster ophthalmic), and malignancies 0.6 (most frequently basal cell carcinoma). At week 105, 269 (44%) patients demonstrated an ACR20 response relative to their respective phase IIb trial baselines. CONCLUSION: Among 319 patients who completed this 2-year extension of two global phase IIb studies, peficitinib 100 mg once daily demonstrated a stable safety profile and sustained effectiveness in patients with moderate-to-severe RA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01711814. Registered 19 October 2012. FUNDING: Astellas Pharma Global Development, Inc.

Targeted drugs in spondyloarthritis during pregnancy and lactation.

Spondyloarthritis (SpA) are a heterogeneous group of chronic inflammatory joint diseases that includes several clinical subgroups. SpA can affect women in the reproductive stage so pregnancy can influence the course of the disease and SpA can affect the maternal-fetal outcome. The treatment of SpA has changed dramatically in recent years and the use of targeted drugs is part of therapeutic armamentarium. The use of targeted drugs during pregnancy is controversial because the information available on safety during this period is still limited. Several cytokines have an important role in the normal development of pregnancy or other cytokines may play a role in certain maternal-fetal complications. Potentially targeted drugs can affect the function of these cytokines during pregnancy. The aim of this study is to review the interrelationship between SpA during pregnancy and lactation, the role of some cytokines during normal pregnancy and the development of maternal-fetal complications as well as to review recent information on targeted drugs during pregnancy and breastfeeding in these patients in order to maximize their use in these critical periods of life.

Polimorfismo -1123G mayor que C en el gen PTPN22 y anticuerpos antipéptido citrulinado cíclico en la artritis reumatoide / PTPN22 -1123G is greater than C polymorphism and anti-cyclic citrullinated protein antibodies in rheumatoid arthritis

Introducción y objetivos: El gen de la proteína tirosina fosfatasa no receptora de tipo 22 (PTPN22) codifica la proteína linfoide tirosina fosfatasa -Lyp-, un importante regulador negativo de la activación de células T, que se ha asociado a distintos trastornos autoinmunitarios. El polimorfismo -1123G>C en el gen PTPN22 parece afectar al control de la transcripción de este gen, pero hasta la fecha, la importancia biológica sobre su contribución al riesgo de desarrollar artritis reumatoide (AR) sigue siendo desconocida. En el presente estudio evaluamos la asociación del polimorfismo -1123G>C con anti-cyclic citrullinated protein antibodies (anti-CCP, «anticuerpos antipéptido citrulinado cíclico») y el riesgo de desarrollar AR en la población del occidente de México. Materiales y métodos: Se realizó un estudio transversal analítico, en el que participaron 300 pacientes con AR clasificados de acuerdo con los criterios del ACR-EULAR y 300 sujetos control (SC). El polimorfismo -1123 G>C se genotipificó mediante PCR-RFLP. Los niveles de anticuerpos anti-CCP fueron cuantificados mediante una prueba de ELISA. Resultados: Encontramos una mayor prevalencia de genotipos homocigotos CC en SC en comparación con los pacientes con AR (OR 0,41; intervalo de confianza del 95% 0,24-0,71; p=0,001), lo que demuestra un posible efecto protector contra la AR. En cuanto a los niveles de anti-CCP, los portadores del genotipo CC mostraron los niveles más bajos en el grupo de AR (p<0,05). Conclusión: El genotipo CC del polimorfismo -1123G>C en el gen PTPN22 es un factor protector para la AR en la población mestiza mexicana y se asocia con niveles bajos de anticuerpos anti-CCP (AU)

Background and objectives: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase -Lyp- and has been associated with different autoimmune disorders. The PTPN22 -1123G>C polymorphism appears to affect the transcriptional control of this gene, but to date, the biological significance of this polymorphisms on rheumatoid arthritis (RA) risk remains unknown. We evaluate the association of PTPN22 -1123G>C polymorphism with anti-cyclic citrullinated protein antibodies (anti-CCP) and risk for RA in population from Western Mexico. Material and methods: A transversal analytic study, which enrolled 300 RA patients classified according to ACR-EULAR criteria and 300 control subjects (CS) was conducted. The -1123 G>C polymorphism was genotyped by PCR-RFLP. The anti-CCP antibodies levels were quantified by ELISA kit. Results: We found a higher prevalence of homozygous PTPN22 -1123CC genotype in CS than in RA patients (OR 0.41; 95% confidence interval 0.24-0.71; P=.001), suggesting a potential protective effect against RA. Concerning anti-CCP levels, the CC genotype carriers showed the lowest median levels in RA (P<.05).Conclusion: The PTPN22 -1123CC genotype is a protector factor to RA in a Mexican-mestizo population and is associated with low anti-CCP antibodies (AU)

PTPN22 -1123G>C polymorphism and anti-cyclic citrullinated protein antibodies in rheumatoid arthritis. / Polimorfismo −1123G>C en el gen PTPN22 y anticuerpos antipéptido citrulinado cíclico en la artritis reumatoide.

BACKGROUND AND OBJECTIVES: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase -Lyp- and has been associated with different autoimmune disorders. The PTPN22 -1123G>C polymorphism appears to affect the transcriptional control of this gene, but to date, the biological significance of this polymorphisms on rheumatoid arthritis (RA) risk remains unknown. We evaluate the association of PTPN22 -1123G>C polymorphism with anti-cyclic citrullinated protein antibodies (anti-CCP) and risk for RA in population from Western Mexico. MATERIAL AND METHODS: A transversal analytic study, which enrolled 300 RA patients classified according to ACR-EULAR criteria and 300 control subjects (CS) was conducted. The -1123 G>C polymorphism was genotyped by PCR-RFLP. The anti-CCP antibodies levels were quantified by ELISA kit. RESULTS: We found a higher prevalence of homozygous PTPN22 -1123CC genotype in CS than in RA patients (OR 0.41; 95% confidence interval 0.24-0.71; P=.001), suggesting a potential protective effect against RA. Concerning anti-CCP levels, the CC genotype carriers showed the lowest median levels in RA (P<.05). CONCLUSION: The PTPN22 -1123CC genotype is a protector factor to RA in a Mexican-mestizo population and is associated with low anti-CCP antibodies.

Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study.

OBJECTIVES: To investigate the efficacy and safety of switching from infliximab reference product (RP) to its biosimilar or maintaining biosimilar treatment in patients with ankylosing spondylitis (AS). METHODS: This open-label extension study recruited patients with AS who completed a 54-week, randomised controlled study comparing CT-P13 with RP (PLANETAS). CT-P13 (5 mg/kg) was administered intravenously every 8 weeks from week 62 to week 102. Efficacy end points included the proportion of patients achieving Assessment of SpondyloArthritis international Society (ASAS)20. Antidrug antibodies (ADAs) were measured using an electrochemiluminescent method. Data were analysed for patients treated with CT-P13 in the main PLANETAS study and the extension (maintenance group) and those who were switched to CT-P13 during the extension study (switch group). RESULTS: Overall, 174 (82.9%) of 210 patients who completed the first 54 weeks of PLANETAS and agreed to participate in the extension were enrolled. Among these, 88 were maintained on CT-P13 and 86 were switched to CT-P13 from RP. In these maintenance and switch groups, respectively, ASAS20 response rates at week 102 were 80.7% and 76.9%. ASAS40 and ASAS partial remission were also similar between groups. ADA positivity rates were comparable (week 102: 23.3% vs 27.4%). Adverse events led to treatment discontinuation during the extension study in 3 (3.3%) and 4 (4.8%) patients, respectively. CONCLUSIONS: This is the first study to show that switching from RP to its biosimilar CT-P13 is possible without negative effects on safety or efficacy in patients with AS. In the maintenance group, CT-P13 was effective and well tolerated over 2 years of treatment. TRIAL REGISTRATION NUMBER: NCT01571206; Results.

Macrophage migration inhibitory factor (MIF) promoter polymorphisms (-794 CATT5-8 and -173 G>C): association with MIF and TNFα in psoriatic arthritis.

Psoriatic arthritis (PsA) is an autoimmune disease with a complex interaction of gene and with a dysregulation of pro-inflammatory cytokine such as Macrophage migration Inhibitory Factor (MIF) and Tumor Necrosis Factor-alpha (TNFα). Two polymorphisms identified in the promoter region of the MIF gene have been described: the STR-794 CATT5-8 (rs5844572) and the SNP-173 G>C (rs755622), which are associated with increased MIF levels in circulation and with autoimmune diseases in several populations. In this case-control study we investigated whether commonly occurring functional MIF polymorphisms are associated with PsA susceptibility and clinical variables as well as with MIF and TNFα serum levels in a Mexican-Mestizo population. Genotyping of the -794 CATT5-8 and -173 G>C MIF polymorphisms was performed by PCR and PCR-RFLP respectively in 50 PsA patients and 100 healthy subjects (HS). MIF and TNFα serum levels were determined by ELISA. A significant increase of MIF (PsA: 7.8 vs. HS: 5.25 ng/mL; p < 0.001) and TNFα (PsA: 24.6 vs. HS: 9.9 pg/mL; p < 0.001) levels was found in PsA patients, a significant correlation was observed between MIF and TNFα (r = 0.41; p < 0.01). The 5,6 repeats genotype of the -794 CATT5-8 MIF was associated with protection to PsA (OR = 0.29; CI 0.77-0.98; p = 0.03), and the G/C genotype (OR = 7.5; CI 2.92-21.64; p < 0.001) and the -173*C allele (OR = 2.45; CI 1.43-4.20; p < 0.001) of the -173 G>C MIF were associated with susceptibility to PsA. In conclusion the -173*C allele is associated with susceptibility to PsA in Mexican-Mestizo population, whereas the correlation between MIF and TNFα soluble levels provided evidence that both cytokines are closely related in the pathophysiology of the PsA.

Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy.

INTRODUCTION: Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy. METHODS: Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR. RESULTS: Among 212 patients randomized in the RCTs, 155 (73%) had ≥ 1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo). CONCLUSIONS: Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy. TRIAL REGISTRATIONS: NCT00325195, NCT01356498.

The -319C/+49G/CT60G haplotype of CTLA-4 gene confers susceptibility to rheumatoid arthritis in Mexican population.

Several single nucleotide polymorphisms (SNPs) within the CTLA-4 gene and elevated serum levels of soluble CTLA-4 (sCTLA-4) have been associated with autoimmunity including rheumatoid arthritis (RA). In this case-control study, we evaluated the relationship between the -319C/T (rs5742909) and CT60 G/A (rs3087243) SNPs and sCTLA-4 levels in 200 RA patients and 200 control subjects (CS) from Western Mexico. Both SNPs were genotyped with the polymerase chain reaction-restriction fragment length polymorphism technique and the sCTLA-4 levels were quantified using an enzyme-linked immunosorbent assay kit. In addition, we performed a haplotype analysis, including our previous data of the +49A/G (rs231775) SNP. The G/A genotype of the rs3087243 SNP was associated with a decreased risk of RA [odd ratio (OR) 0.61, 95% confidence interval (CI) 0.38-0.96, p = 0.024]. This protection was also observed in the negative anti-cyclic citrullinated peptide group of RA carriers of the A allele (OR 0.48, 95% CI 0.22-1.05, p = 0.042). On the contrary, we identified the -319C/+49G/CT60G haplotype of CTLA-4 gene as a risk factor for RA (OR 1.69, 95% CI 1.13-2.52, p = 0.01). The sCTLA-4 levels were not associated with RA (p = 0.377), but were correlated with the functional disability of these patients (r = 0.282, p = 0.012). However, in CS the C/T genotype of the rs5742909 SNP, as well as the G/G and G/A genotypes of the rs3087243 SNP were associated with higher sCTLA-4 levels (p < 0.001). In conclusion, our results suggest that the -319C/+49G/CT60G haplotype of CTLA-4 gene is a genetic marker of susceptibility to RA in Western Mexico, whereas the rs3087243 SNP confers protection against this disease. Moreover, both SNPs showed an effect on the sCTLA-4 production in our control population. However, further studies are required to evaluate the role of sCTLA-4 in RA, as well as the molecular and functional basis of the association between both CTLA-4 gene SNPs and soluble levels of CTLA-4 in CS.

A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study.

OBJECTIVES: To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS). METHODS: Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed. RESULTS: Geometric mean AUC was 32 765.8 µgh/ml for CT-P13 and 31 359.3 µgh/ml for INX. Geometric mean Cmax,ss was 147.0 µg/ml for CT-P13 and 144.8 µg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively. CONCLUSIONS: The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30.