Impact of ultrasonography on treatment decision in rheumatoid arthritis: the IMPULSAR study.

Ultrasonography (US) has shown to be more sensitive than physical examination for diagnosis and assessment of rheumatoid arthritis (RA). It is also a useful approach for accurate monitoring and intensive treatment adjustment. However, there is limited information concerning the impact of US on therapeutic decision-making in routine daily practice. A single-center cross-sectional study in routine daily practice was conducted to determine the percentage of patients with rheumatoid arthritis (RA) in which treatment decision was modified on the basis of results of musculoskeletal ultrasonography. All consecutive patients with RA visited for the control of their disease between September and November 2014 were included. Patients were visited by their attending rheumatologist, who made a therapeutic decision according to the results of physical examination and laboratory tests. Thereafter, a musculoskeletal ultrasound (US) was performed by an independent expert sonographer. According to US findings, a change in therapeutic decision was considered, and categorized as 'negative' (maintenance of the therapeutic attitude) or 'positive' (intensification or reduction of treatment). A total of 78 patients (83% women, mean age 63.3 years) were included. In 29 patients [32%, 95% confidence interval (CI) 26.5-48.9], a change in the therapeutic decision was made, which included intensification of treatment in 18 (62.1%) and reduction of treatment in 11 (37.9%). Change of treatment was more frequent in patients with intermediate disease activity (low and moderate) than in those in clinical remission or with high activity (41.4 vs. 25%), in men than in women (53.8 vs. 33.8%), and in the presence than in the absence of bone erosions (43.6 vs. 21.7%), although differences were not statistically significant. We conclude that in patients with RA, joint US is a relevant complementary tool for treatment decisions in daily practice, particularly in patients with intermediate disease activity.

Estudio VARIAR: valoración de la eficacia y seguridad a corto plazo en artritis reumatoide del uso de RItuximab comparado con Antagonistas del factor de necrosis tumoral alfa en segunda línea terapéutica en pacientes con artritis reumatoide Refractarios a un primer antagonista del factor de necrosis tumoral alfa / VARIAR Study: assessment of short-term efficacy and safety of rituximab compared to an tumor necrosis factor alpha antagonists as second-line drug therapy in patients with rheumatoid arthritis refractory to a first tumor necrosis factor alpha antagonist

Objetivo. Evaluar la eficacia y la seguridad a corto plazo del tratamiento de pacientes con artritis reumatoide (AR) con rituximab (RTX) comparado con un anti-TNF (2TNF) tras retirada de un primer anti-TNF. Métodos. Estudio multicéntrico prospectivo, observacional, de práctica clínica de pacientes con AR grave refractaria a anti-TNF que recibieron RTX comparados con los que recibieron un 2TNF. Comparación de las variables de eficacia y respuesta EULAR buena/moderada a los 6 meses. Resultados. Ciento tres pacientes incluidos; 82 alcanzan seguimiento a 6 meses, 73,7% mujeres. Datos basales grupo RTX y 2TNF, respectivamente: 8,6 y 6,6 NAD, 8,8 y 7,5 NAI, 5,45 ± 1,28 y 5,18 ± 1,21 en DAS28 (p=0,048), 41 y 38,7mmHg de VSG, y 1,2 y 1,0 en HAQ. Mejoría en todos los parámetros en ambos grupos sin diferencias significativas (excepto mayor reducción de VSG con RTX). Ausencia de efectos adversos graves. Conclusiones. El uso de RTX en segunda línea de terapia biológica tras fallo a un primer anti-TNF en práctica clínica muestra mejoría en las variables de eficacia y funcionalidad a los 6 meses, sin presentar efectos adversos graves. Estos resultados no difieren de los observados tras el uso de un segundo anti-TNF en el mismo escenario clínico (AU)

Objective. to compare the short-term efficacy and safety of rituximab (RTX) therapy versus anti-TNF in rheumatoid arthritis (RA) patients after discontinuation of a first anti-TNF agent. Methods. prospective observational multicenter study in the clinical practice setting, involving patients with severe RA refractory to a first anti-TNF agent, who received either RTX or a second anti-TNF (2TNF), comparing the efficacy endpoints, EULAR response (Good/Moderate) and safety at 6 months. Results. 103 patients enrolled, 82 completed 6-month follow-up, 73.7% women. Baseline data for RTX and 2TNF groups, respectively: TJC, 8.6 and 6.6; SJC, 8.8 and 7.5; DAS28 score, 5.45 (±1.28) and 5.18 (±1.21) (p=0.048), ESR, 41 and 38.7mmHg; and HAQ, 1.2 and 1.0. Improvement was observed in all parameters, with no significant differences (except for a more marked reduction in ESR with RTX). There were no serious adverse events. Conclusions. RTX use as second-line therapy after anti-TNF failure led to improvements in the efficacy and functional variables at 6 months, with no serious adverse events. These results were comparable to those observed in patients who used a second anti-TNF agent in the same clinical scenario (AU)

VARIAR Study: Assessment of short-term efficacy and safety of rituximab compared to an tumor necrosis factor alpha antagonists as second-line drug therapy in patients with rheumatoid arthritis refractory to a first tumor necrosis factor alpha antagonist. / Estudio VARIAR: VAloración de la eficacia y seguridad a corto plazo en artritis reumatoide del uso de RItuximab comparado con Antagonistas del factor de necrosis tumoral alfa en segunda línea terapéutica en pacientes con artritis reumatoide Refractarios a un primer antagonista del factor de necrosis tumoral alfa.

OBJECTIVE: to compare the short-term efficacy and safety of rituximab (RTX) therapy versus anti-TNF in rheumatoid arthritis (RA) patients after discontinuation of a first anti-TNF agent. METHODS: prospective observational multicenter study in the clinical practice setting, involving patients with severe RA refractory to a first anti-TNF agent, who received either RTX or a second anti-TNF (2TNF), comparing the efficacy endpoints, EULAR response (Good/Moderate) and safety at 6 months. RESULTS: 103 patients enrolled, 82 completed 6-month follow-up, 73.7% women. Baseline data for RTX and 2TNF groups, respectively: TJC, 8.6 and 6.6; SJC, 8.8 and 7.5; DAS28 score, 5.45 (±1.28) and 5.18 (±1.21) (p=0.048), ESR, 41 and 38.7mmHg; and HAQ, 1.2 and 1.0. Improvement was observed in all parameters, with no significant differences (except for a more marked reduction in ESR with RTX). There were no serious adverse events. CONCLUSIONS: RTX use as second-line therapy after anti-TNF failure led to improvements in the efficacy and functional variables at 6 months, with no serious adverse events. These results were comparable to those observed in patients who used a second anti-TNF agent in the same clinical scenario.

Association between nailfold capillaroscopy findings and pulmonary function tests in patients with systemic sclerosis.

OBJECTIVE: To determine whether there is an association between different capillaroscopic findings and pulmonary function tests in systemic sclerosis (SSc). METHODS: We did a retrospective observational study in a cohort of patients with SSc and early SSc. Patients with at least 1 nailfold videocapillaroscopy (NVC) magnified 120× were included. Pathological findings were giant capillaries, angiogenesis, and density loss. Findings were compared with lung function values: percent expected value of forced vital capacity (FVC), DLCO, and FVC/DLCO ratio. Other variables collected were sex and SSc type, and the presence of digital ulcers (DU), interstitial lung disease (ILD), scleroderma renal crisis, and/or pulmonary hypertension (PH). RESULTS: Of 136 patients with SSc, 85 had undergone an NVC. The frequency of ILD, DU, and PH was 24.1%, 28.7%, and 17.2%, respectively. Data analysis showed that patients with density loss had worse FVC% (86.91 ± 19.42 vs 101.13 ± 16.06, p < 0.01) and DLCO% (71.43 ± 21.19 vs 85.9 ± 19.81, p < 0.01) compared to those without. CONCLUSION: Patients with loss of density present worse FVC and DLCO values. Prospective studies are warranted to determine whether NVC is useful for studying pulmonary function in SSc.

Adalimumab regulates intracellular TNFα production in patients with rheumatoid arthritis.

INTRODUCTION: Adalimumab is a fully human anti-tumor necrosis factor α (anti-TNFα) monoclonal antibody that specifically blocks the interaction of TNFα with its receptors. It binds both soluble and transmembrane TNFα. We hypothesized that blocking these TNFα signals regulates the altered TNFα production in rheumatoid arthritis (RA) patients. METHODS: We compared, by flow cytometry, Toll-like receptor induction levels of membrane and intracellular TNFα in monocytes (iTNFα + CD14+ cells) from 12 patients before and after adalimumab treatment with those from 5 healthy donors. RESULTS: Before starting the treatment, the percentage of iTNFα+ CD14+ cells in the RA patients was significantly lower than that in healthy donors (mean ± SEM = 33.16 ± 4.82% vs 66.51 ± 2.4%, P < 0.001). When we added in vitro TNFα to healthy donor culture cells, levels of iTNFα+ CD14+ cells decreased, suggesting that the TNFα signal was responsible for the iTNFα+ CD14+ cell downregulation observed in the RA patients. After 2, 6 and 12 adalimumab injections, we observed significant blocking of membrane and soluble TNFα and a progressive increase in iTNFα+ CD14+ cells in ten patients with a good to moderate response as defined by the European League Against Rheumatism (EULAR) criteria. Levels of iTNFα+ CD14+ cells after 12 injections in these 10 patients were comparable to levels in healthy donors. In two patients, iTNFα+ CD14+ cell upregulation was not observed, and their EULAR-defined responses had not improved. The first patient developed antiadalimumab antibodies, explaining why adalimumab was not able to block membrane and soluble TNFα. In the second patient, adalimumab was discontinued because of adverse effects, which led to a decrease in iTNFα+ CD14+ cells to levels measured before treatment. CONCLUSIONS: Our findings suggest that adalimumab treatment in RA patients can return iTNFα levels to those of healthy donors. This effect was not observed in the presence of neutralizing antiadalimumab antibodies.

Rituximab-induced interleukin-15 reduction associated with clinical improvement in rheumatoid arthritis.

Rituximab therapy alters all aspects of B-cell participation in the disturbed immune response of rheumatoid arthritis patients. To determine the impact of B-cell depletion on other immune compartments, we analysed levels of soluble and surface interleukin-15 (IL-15) along with the frequency of IL-15-related subsets after rituximab treatment. We then studied the correlation of observed changes with clinical activity. Heparinized blood samples from 33 rheumatoid arthritis patients were collected on days 0, 30, 90 and 180 after each of three rituximab cycles. Serum cytokine levels were determined by ELISA. Interleukin-15 trans-presentation was analysed by cytometry. Flow cytometry with monoclonal antibodies was performed to analyse circulating cell subsets. Interleukin-15 was detected in the serum of 25 patients before initiating the treatment. Rituximab then progressively reduced serum IL-15 (138 ± 21 pg/ml at baseline, 48 ± 18 pg/ml after third cycle, P = 0·03) along with IL-17 (1197 ± 203 pg/ml at baseline, 623 ± 213 pg/ml after third cycle, P = 0·03) and tended to increase the frequency of circulating regulatory T cells (3·1 ± 1 cells/µl at baseline, 7·7 ± 2 cells/µl after third cycle). Rituximab also significantly decreased IL-15 trans-presentation on surface monocytes of patients negative for IL-15 serum (mean fluorescence intensity: 4·82 ± 1·30 at baseline, 1·42 ± 0·69 after third cycle P = 0·05). Reduction of serum IL-15 was associated with decrease in CD8(+)  CD45RO(+) /RA(+) ratio (1·17 ± 0·21 at baseline, 0·36 ± 0·06 at third cycle, P = 0·02). DAS28, erythrocyte sedimentation rate and C-reactive protein correlated significantly with CD8(+)  CD45RO(+) /RA(+) ratio (R = 0·323, R = 0·357, R = 0·369 respectively, P < 0·001). Our results suggest that sustained clinical improvement after rituximab treatment is associated with IL-15/memory T-cell-related mechanisms beyond circulating B cells.

Ustekinumab treatment of TNF antagonist-induced paradoxical psoriasis flare in a patient with psoriatic arthritis: case report and review.

BACKGROUND: Therapy with tumour necrosis factor α (TNF) inhibitors can be associated with paradoxical reactions, namely the de novo development or flaring of conditions that usually respond to these therapeutic agents, such as arthritis, inflammatory bowel disease, sarcoidosis or psoriasis. They are considered a class effect of these drugs, and their incidence ranges from 1 to 5%, with paradoxical psoriasis (psoriasis vulgaris, palmoplantar pustulosis, scalp psoriasis and their combinations) being most frequently reported. Treatment of paradoxical psoriasis often requires withdrawal of the inducing drug and switching to another anti-TNF agent, but often this cannot avoid recurrence or persistence of the rash and/or loss of the therapeutic effect on the underlying condition. CASE REPORT: We report on a 47-year-old woman who developed incapacitating palmoplantar pustulosis and psoriasis vulgaris flare with severe scalp and nail involvement after 5 months of treatment with adalimumab for psoriatic arthritis. Several treatments, including topical corticosteroids, photochemotherapy, ciclosporin, acitretin and etanercept 50 mg twice a day for 1 month, were ineffective or not tolerated. Treatment with ustekinumab 45 mg provided complete resolution of skin lesions with acceptable therapeutic control of the arthritis, with a follow-up duration of 16 months. CONCLUSION: A review of the reported cases suggests that this may be a therapeutic option in patients who develop paradoxical psoriasis while under treatment for arthritis or Crohn's disease.

Inflamación bronquial, clínica respiratoria y función pulmonar en el síndrome de Sjögren primario / Bronchial Inflammation, Respiratory Symptoms and Lung Function in Primary Sjögren’s Syndrome

Introducción: En el síndrome de Sjögren primario (SSp) no se dispone de información suficiente queanalice la relación entre la clínica respiratoria o la función pulmonar y la inflamación bronquial presente,medida por esputo inducido.Objetivo: Descripción de las características clínicas y de función pulmonar en los pacientes diagnosticadosde SSp y su relación con el perfil inflamatorio de la luz bronquial.Métodos: Se analizaron síntomas respiratorios, radiología, función pulmonar, hiperrespuesta bronquiale inflamación mediante esputo inducido de 36 pacientes consecutivos diagnosticados de SSp.Resultados: El 58% de los pacientes presentó carraspera y el 42% tos y disnea. No hubo alteraciones destacablesde la función pulmonar, pero el 46% (n = 16) presentó una prueba de respuesta bronquial positiva.La linfocitosis > 2,6% en esputo estaba presente en el 69% de los esputos analizados. Presentaron toscrónica el 29% de los pacientes con linfocitosis (n = 24), frente al 73% de los normales (n = 11) (p = 0,02),con una duración de la tos inferior para el primero (p = 0,02). Por el contrario, la hiperrespuesta bronquialse asoció con linfocitosis (p = 0,02). El 55% de los esputos patológicos (n = 22) presentaron lipófagos(índice > 15) frente al 18% de los normales (n = 11) (p = 0,05).Conclusión: Los síntomas respiratorios (carraspera, tos y disnea) son frecuentes en el SSp aunque surelación con la hiperrespuesta bronquial y la inflamación de la vía aérea es variable. El hallazgo de linfocitosisen la vía aérea constituye un foco infiltrativo más de la enfermedad, siendo el esputo inducidouna herramienta complementaria en la valoración de la actividad inflamatoria pulmonar del SSp(AU)

Introduction: There is no information available regarding the relationship between the respiratory symptomsor lung function and bronchial inflammation, measured by induced sputum.Objectives: Description of the clinical characteristics, radiographic images and lung function of patientssuffering from Primary Sjögren Syndrome (PSS), and to assess the relationship with the inflammatoryairway profile.Methods: Weanalysed clinical, radiology, lung function tests, bronchial hyperresponsiveness and inflammatorydata in the induced sputum from 36 consecutive patients with PSS.Results: A total of 58% of patients had hoarseness and 42% had cough and dispnea. No lung dysfunctionwas observed, although 46% (n = 16) had a positive bronchial response. Lymphocytosis >2.6% in inducedsputum was observed in 69% of all sputa. There was chronic coughin 29% of patients with lymphocytosis(n = 24), whereas 73% were normal (n = 11) (P = .02). The duration time of cough was less for the former (P = .02). On the contrary a positive bronchial response was associated with lymphocytosis >2.6% (P = .02). Lipophages were presnt in 55% of pathological sputa (n = 22) (index >15) versus 18% of the non-pathological ones (n = 11) (P = .05). Conclusion: Hoarseness, cough and dyspnea are frequent respiratory symptoms in PSS, although there is awide variation in the relationship with bronchial responsiveness and airway inflammation. Lymphocytosisin the airways is another site of the infiltrative process in PSS, and the induced sputum is a complementarytool in the identification of active inflammatory process(AU)

Bronchial inflammation, respiratory symptoms and lung function in Primary Sjögren's syndrome.

INTRODUCTION: There is no information available regarding the relationship between the respiratory symptoms or lung function and bronchial inflammation, measured by induced sputum. OBJECTIVES: Description of the clinical characteristics, radiographic images and lung function of patients suffering from Primary Sjögren Syndrome (PSS), and to assess the relationship with the inflammatory airway profile. METHODS: We analysed clinical, radiology, lung function tests, bronchial hyperresponsiveness and inflammatory data in the induced sputum from 36 consecutive patients with PSS. RESULTS: A total of 58% of patients had hoarseness and 42% had cough and dispnea. No lung dysfunction was observed, although 46% (n=16) had a positive bronchial response. Lymphocytosis >2.6% in induced sputum was observed in 69% of all sputa. There was chronic cough in 29% of patients with lymphocytosis (n=24), whereas 73% were normal (n=11) (P=.02). The duration time of cough was less for the former (P=.02). On the contrary a positive bronchial response was associated with lymphocytosis >2.6% (P=.02). Lipophages were present in 55% of pathological sputa (n=22) (index >15) versus 18% of the non-pathological ones (n=11) (P=.05). CONCLUSION: Hoarseness, cough and dyspnea are frequent respiratory symptoms in PSS, although there is a wide variation in the relationship with bronchial responsiveness and airway inflammation. Lymphocytosis in the airways is another site of the infiltrative process in PSS, and the induced sputum is a complementary tool in the identification of active inflammatory process.

Are there clinical or serological differences between male and female patients with primary Sjögren's syndrome?

OBJECTIVE: Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease. It can be primary (pSS) or secondary (sSS) and is observed 90% more in women than in men, mainly in the fourth and fifth decades of life. We investigated the prevalence of serological and clinical manifestations in male and female patients with primary SS. METHODS: We analyzed 521 female and 28 male patients with pSS between 1993 and 2001. All patients fulfilled > or = 4 of the 1993 European Community Study Group criteria. RESULTS: Men presented higher concentrations of IgA, rheumatoid factor, and antinuclear antibodies than women. A higher percentage of women than men reported fibromyalgia, thyroidal manifestations, and carpal tunnel syndrome. There were no statistical differences between the 2 groups in relation to the presence of Raynaud's phenomenon, arthritis, erosive osteoarthritis, liver disease, or other visceral manifestations. CONCLUSION: The pattern of SS in our cohort of patients reveals a difference between male and female patients, in contrast with earlier studies.