Withdrawal of infliximab therapy in ankylosing spondylitis in persistent clinical remission, results from the REMINEA study

BackgroundRecent data suggest that anti-TNF doses can be reduced in ankylosing spondylitis (AS) patients. Some authors even propose withdrawing treatment in patients in clinical remission; however, at present there is no evidence to support this.ObjectiveTo assess how long AS patients with persistent clinical remission remained free of flares after anti-TNF withdrawal and to evaluate the effects of treatment reintroduction. We also analyze the characteristics of patients who did not present clinical relapse.MethodsMulticenter, prospective, observational study of a cohort of patients with active AS who had received infliximab as a first anti-TNF treatment and who presented persistent remission (more than 6months). We recorded at baseline and every 6-8weeks over the 12-month period the age, gender, disease duration, peripheral arthritis or enthesitis, HLA-B27 status, BASDAI, CRP, ESR, BASFI, and three visual analogue scales, spine global pain, spinal night time pain, and patient's global assessment.ResultsThirty-six out of 107 patients (34%) presented persistent remission and were included in our study. After treatment withdrawal, 21 of these 36 patients (58%) presented clinical relapse during follow-up. Infliximab therapy was reintroduced and only 52% achieved clinical remission, as they had before the discontinuation of infliximab; in an additional 10%, reintroduction of infliximab was ineffective, obliging us to change the anti-TNF therapy. No clinical or biological factors were associated with the occurrence of relapse during the follow-up.ConclusionsTwo thirds of patients in clinical remission presented clinical relapse shortly after infliximab withdrawal. Although the reintroduction of infliximab treatment was safe, half of the patients did not present the same clinical response that they had achieved prior to treatment withdrawal

Correlation of fatigue with other disease related and psychosocial factors in patients with rheumatoid arthritis treated with tocilizumab: ACT-AXIS study

To assess the hypothesis if tocilizumab (TCZ) is effective on disease activity, and also its effect in fatigue and other clinical and psychological disease-related factors in patients with rheumatoid arthritis (RA) treated with TCZ.A 24-week, multicenter, prospective, observational study in patients with moderate to severe RA receiving TCZ after failure or intolerance to disease-modifying antirheumatic drugs or tumor necrosis factor-alpha was conducted.Of the 122 patients included, 85 were evaluable for effectiveness (85% female, 51.9 ± 12.5 years, disease duration 8.7 ± 7.4 years). Mean change in C-reactive protein level from baseline to week 12 was -11.2 ± 4.0 (P < .001). Mean Disease Activity Index score (DAS28) decreased from 5.5 ± 1.0 at baseline to 2.7 ± 1.3 (P < .001) at week 24. Mean change in Functional Assessment of Chronic Illness Therapy score was -5.4 ± 11.2 points at week 24. Multiple regression analysis showed that the improvement in DAS28, sleep, and depression explained 56% and 47% of fatigue variance at week 12 and 24, respectively.Tocilizumab is effective in reducing disease activity and results in a clinically significant improvement in fatigue, pain, swollen joint count, morning stiffness, sleepiness, depression, and DAS28; the last 3 were specifically identified as factors explaining fatigue variance with the use of TCZ in RA patients

Tuberculosis in pediatric patients treated with anti-TNFα drugs: a cohort study

Background: Adult patients receiving anti-TNFα drugs are at increased risk of tuberculosis (TB), but studies in pediatric populations are limited, and the best strategy for latent tuberculosis infection (LTBI) screening in this population remains controversial. We describe the prevalence of LTBI prior to anti-TNFα therapy and the long-term follow-up after biological treatment initiation in a cohort of children and adolescents. Methods: Cohort observational study in children and adolescents receiving anti-TNFα agents in a tertiary-care pediatric hospital. LTBI was ruled out prior to the implementation of anti-TNFα drugs by tuberculin skin test (TST), and, from March 2012 on, QuantiFERON Gold-In Tube® test (QTF-G). During anti-TNFα treatment, patients were evaluated every 6 months for TB with history and physical examination. TST/QTF-G were not repeated unless signs or symptoms consistent with TB arose or there was proven TB contact. Results: The final cohort consisted of 221 patients (56.1 % female; 261 treatments), of whom 51.7 %/30.0 %/17.3 % were treated with etanercept/adalimumab/infliximab, respectively, for a variety of rheumatic diseases (75.6 %), inflammatory bowel disease (20.8 %), and inflammatory eye diseases (3.6 %). The median (IQR) age at diagnosis of the primary condition was 6.8 years (2.7-11.0) and the duration of the disease before implementing the anti-TNFα agent was 1.8 years (0.6-4.2). LTBI was diagnosed in 3 adolescent girls (prevalence rate: 1.4 %; 95 % CI: 0.4-4.2) affected with juvenile idiopathic arthritis: TST tested positive in only 1, while QTF-G was positive in all cases (including 2 patients already on etanercept). They all received antiTB chemoprophylaxis and were later (re)treated with etanercept for 24-29 months, without incidences. No incident cases of TB disease were observed during the follow-up period under anti-TNFα treatment of 641 patients-year, with a median (IQR) time per patient of 2.3 years (1.4-4.3). Conclusions: In our study, the prevalence of LTBI (1.4 %) was similar to that reported in population screening studies in Spain; no incident cases of TB disease were observed. In low-burden TB settings, initial screening for TB in children prior to anti-TNFα treatment should include both TST and an IGRA test, but systematic repetition of LTBI immunodiagnostic tests seems unnecessary in the absence of symptoms or known TB contact

Body mass index and disease activity in chronic inflammatory rheumatic diseases: results of the Cardiovascular in Rheumatology (Carma) Project

Objective: Since obesity has been associated with a higher inflammatory burden and worse response to therapy in patients with chronic inflammatory rheumatic diseases (CIRD), we aimed to confirm the potential association between body mass index (BMI) and disease activity in a large series of patients with CIRDs included in the Spanish CARdiovascular in rheuMAtology (CARMA) registry. Methods: Baseline data analysis of patients included from the CARMA project, a 10-year prospective study of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) attending outpatient rheumatology clinics from 67 Spanish hospitals. Obesity was defined when BMI (kg/m2) was >30 according to the WHO criteria. Scores used to evaluate disease activity were Disease Activity Score of 28 joints (DAS28) in RA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS, and modified DAS for PsA. Results: Data from 2234 patients (775 RA, 738 AS, and 721 PsA) were assessed. The mean ± SD BMI at the baseline visit were: 26.9 ± 4.8 in RA, 27.4 ± 4.4 in AS, and 28.2 ± 4.7 in PsA. A positive association between BMI and disease activity in patients with RA (β = 0.029; 95%CI (0.01- 0.05); p = 0.007) and PsA (β = 0.036; 95%CI (0.015-0.058); p = 0.001) but not in those with AS (β = 0.001; 95%CI (-0.03-0.03); p = 0.926) was found. Disease activity was associated with female sex and rheumatoid factor in RA and with Psoriasis Area Severity Index and enthesitis in PsA. Conclusions: BMI is associated with disease activity in RA and PsA, but not in AS. Given that obesity is a potentially modifiable factor, adequate control of body weight can improve the outcome of patients with CIRD and, therefore, weight control should be included in the management strategy of these patients

Estudi del dolor múscul-esquelètic en dos categories diferenciades de pacients amb lupus eritematós sistèmic sense signes inflamatoris a l’exploració física: artro-miàlgies generalitzades i artràlgies inflamatòries a mans

En aquesta Tesi Doctoral he analitzat diferents manifestacions múscul-esquelètiques que sovint manifesten els pacients amb Lupus Eritematós Sistèmic, en una àrea metropolitana Mediterrània. Per una banda hem estudiat als pacients amb símptomes de dolor osteoarticular generalitzat, i per una altra banda hem estudiat als pacients amb dolor articular a mans de ritme inflamatori. Tant en un grup de pacients com en l’altre, l’exploració física no mostrava signes inflamatoris suggestius d’activitat de la malaltia lúpica. En primer lloc, l’estudi d’artromiàlgies generalitzades (compatible amb fibromiàlgia) en pacients amb Lupus Eritematós Sistèmic planteja els següents objectius: a) establir la prevalença de clínica compatible amb fibromiàlgia, i de clínica suggestiva d’ansietat i de depressió; b) establir-ne la relació entre ells; c) demostrar l’absència de relació amb l’activitat de la malaltia lúpica, i avaluar-ne la percepció de qualitat de vida i discapacitat associades. En segon lloc, l’estudi de les artràlgies inflamatòries a mans en pacients amb Lupus Eritematós Sistèmic em plantejà els objectius següents: a) establir la relació entre la presència d’artràlgies inflamatòries i la presència d’alteracions inflamatòries a nivell ecogràfic; b) descriure’n les troballes; c) demostrar-ne l’associació amb l’activitat de la malaltia lúpica, i avaluar-ne la percepció de qualitat de vida i discapacitat associades. La metodologia emprada va ser similar en ambdós treballs. A partir d’una població de pacients amb Lupus Eritematós Sistèmic, vam definir els criteris d’inclusió en funció de la simptomatologia a estudi. En tots els participants, inclosos consecutivament, se’ls va realitzar l’anamnesi i l’exploració física acurades, se’ls van realitzar qüestionaris d’activitat, qualitat de vida, discapacitat, ansietat i depressió, se’ls practicaren anàlisis rutinaris amb les principals mesures d’activitat, i se’ls van avaluar ecogràficament les articulacions de les mans (en el segon treball). Totes les dades es van registrar i analitzar posteriorment a la recollida transversal que es va fer de totes elles en un mateix temps de forma individual, al llarg dels anys 2005 a 2009. El primer treball va comparar la presència de fibromiàlgia entre pacients amb Lupus Eritematós Sistèmic, i posteriorment va analitzar les diferents associacions a estudi, i es van comparar amb els pacients que no presentaven fibromiàlgia. En el segon treball es van comparar pacients amb Lupus Eritematós Sistèmic amb artràlgies a mans amb aquells que no les presentaven. Amb tot, es van recollir dades de 84 pacients per al primer treball, i de 58 per al segon, que han estat publicades en dos articles científics de revistes de l’àrea de la Reumatologia. Les conclusions a les que he arribat són les següents: En pacients amb Lupus Eritematós Sistèmic, la prevalença de Fibromiàlgia és del 35.7%, la d’Ansietat del 35.7% i la de Depressió del 19%. S’estableix una relació entre la presència de Fibromiàlgia i la d’Ansietat i/o Depressió, sense observar relació amb una major activitat de la malaltia lúpica, produint una pitjor percepció de la qualitat de vida tant en el seu domini físic com en el mental. En pacients amb Lupus Eritematós Sistèmic hem observat una relació entre la presència d’artràlgies inflamatòries i rigidesa matutina a articulacions de les mans i la presència d’alteracions ecogràfiques, fins al 71.4% d’aquests pacients, essent-ne les més freqüents: tenosinovitis de d’extensors, vessament a l’articulació ràdio-carpiana, senyal Doppler positiva, sinovitis a l’articulació ràdio-carpiana, vessament a articulacions metacarp-falàngiques, vessament a articulacions interfalàngiques proximals, tenosinovitis de flexors. Aquestes alteracions s’associen a la presència de major activitat lúpica, produint una pitjor percepció de la qualitat de vida en el seu domini físic, però no en el mental, i produint una tendència a presentar major discapacitat.This Doctoral Thesis I have completed, I assessed several musculoskeletal manifestations that patients with Systemic Lupus Erythematosus patients from a metropolitan and Mediterranean region often complain. I studied two kind of patients, those with widespread musculoskeletal pain and those with hand and wrist inflammatory arthralgia. Both types of patients did not show inflammatory signs at physical exam. In the study of patients with widespread pain (fibromyalgia-like symptoms) I aimed the following objectives: to establish fibromyalgia, anxiety and depression prevalence; to assess the relationship between them; to demonstrate the absence of lupus activity in these patients and to assess the associated quality of life and disability. In the study of the inflammatory hand and wrist arthralgia I aimed the following objectives: to establish its relationship with the presence of ultrasound abnormalities; to describe these abnormalities; to demonstrate its association to lupus activity, and to assess the associated quality of life and disability. The methodology used was similar in both projects. I studied a well defined and controlled Systemic Lupus Erythematosus patient’s cohort, and I defined inclusion criteria based on the symptoms aimed to evaluate. All participants were included consecutively after careful clinical interrogatory and physical exam. Patients and I fulfilled several activity, quality of life, disability, and psychiatric disorders questionnaires. They also received routine blood tests assessing main activity markers, and, in the second project, they were assessed by joint ultrasound at both hands. All data were registered and analysed after the cross-sectional intervention, through 2005-2009. The first work also compared data with lupus patients without fibromyalgia, and the second work compared data with lupus patients without hand and wrist arthralgia. A total of 84 patients were assessed in the study of widespread pain, and 58 were included in the study of hand and wrist arthralgia. Results were published in two different original articles in two scientific Rheumatology journals each. Conclusions: Patients with Systemic Lupus Erythematosus from a metropolitan and Mediterranean area showed a prevalence of 35.7% of both fibromyalgia and anxiety and 19% of depression. An association between the presence of fibromyalgia and psychiatric disorders was observed. No relationship to lupus disease activity was observed. Patients with fibromyalgia showed both mental and physical poorer quality of life. In patients with Systemic Lupus Erythematosus from a metropolitan and Mediterranean area a relationship between the presence of inflammatory hand and wrist arthralgia and the presence of ultrasound abnormalities was observed in up to 71.4%. The main ultrasound abnormalities observed were digital extensorum tenosynovitis, radio-carpal joint effusion, positive Doppler signal, radio-carpal joint synovitis, proximal interphalangeal joints effusion and digital flexorum tenosynovitis. These ultrasound abnormalities were associated to the presence of higher lupus activity, poorer physical quality of life (not mental) and a trend to higher disability

Estudi del dolor múscul-esquelètic en dos categories diferenciades de pacients amb lupus eritematós sistèmic sense signes inflamatoris a l'exploració física: artro-miàlgies generalitzades i artràlgies inflamatòries a mans

En aquesta Tesi Doctoral he analitzat diferents manifestacions múscul-esquelètiques que sovint manifesten els pacients amb Lupus Eritematós Sistèmic, en una àrea metropolitana Mediterrània. Per una banda hem estudiat als pacients amb símptomes de dolor osteoarticular generalitzat, i per una altra banda hem estudiat als pacients amb dolor articular a mans de ritme inflamatori. Tant en un grup de pacients com en l'altre, l'exploració física no mostrava signes inflamatoris suggestius d'activitat de la malaltia lúpica. En primer lloc, l'estudi d'artromiàlgies generalitzades (compatible amb fibromiàlgia) en pacients amb Lupus Eritematós Sistèmic planteja els següents objectius: a) establir la prevalença de clínica compatible amb fibromiàlgia, i de clínica suggestiva d'ansietat i de depressió; b) establir-ne la relació entre ells; c) demostrar l'absència de relació amb l'activitat de la malaltia lúpica, i avaluar-ne la percepció de qualitat de vida i discapacitat associades. En segon lloc, l'estudi de les artràlgies inflamatòries a mans en pacients amb Lupus Eritematós Sistèmic em plantejà els objectius següents: a) establir la relació entre la presència d'artràlgies inflamatòries i la presència d'alteracions inflamatòries a nivell ecogràfic; b) descriure'n les troballes; c) demostrar-ne l'associació amb l'activitat de la malaltia lúpica, i avaluar-ne la percepció de qualitat de vida i discapacitat associades. La metodologia emprada va ser similar en ambdós treballs. A partir d'una població de pacients amb Lupus Eritematós Sistèmic, vam definir els criteris d'inclusió en funció de la simptomatologia a estudi. En tots els participants, inclosos consecutivament, se'ls va realitzar l'anamnesi i l'exploració física acurades, se'ls van realitzar qüestionaris d'activitat, qualitat de vida, discapacitat, ansietat i depressió, se'ls practicaren anàlisis rutinaris amb les principals mesures d'activitat, i se'ls van avaluar ecogràficament les articulacions de les mans (en el segon treball). Totes les dades es van registrar i analitzar posteriorment a la recollida transversal que es va fer de totes elles en un mateix temps de forma individual, al llarg dels anys 2005 a 2009. El primer treball va comparar la presència de fibromiàlgia entre pacients amb Lupus Eritematós Sistèmic, i posteriorment va analitzar les diferents associacions a estudi, i es van comparar amb els pacients que no presentaven fibromiàlgia. En el segon treball es van comparar pacients amb Lupus Eritematós Sistèmic amb artràlgies a mans amb aquells que no les presentaven. Amb tot, es van recollir dades de 84 pacients per al primer treball, i de 58 per al segon, que han estat publicades en dos articles científics de revistes de l'àrea de la Reumatologia. Les conclusions a les que he arribat són les següents: En pacients amb Lupus Eritematós Sistèmic, la prevalença de Fibromiàlgia és del 35.7%, la d'Ansietat del 35.7% i la de Depressió del 19%. S'estableix una relació entre la presència de Fibromiàlgia i la d'Ansietat i/o Depressió, sense observar relació amb una major activitat de la malaltia lúpica, produint una pitjor percepció de la qualitat de vida tant en el seu domini físic com en el mental. En pacients amb Lupus Eritematós Sistèmic hem observat una relació entre la presència d'artràlgies inflamatòries i rigidesa matutina a articulacions de les mans i la presència d'alteracions ecogràfiques, fins al 71.4% d'aquests pacients, essent-ne les més freqüents: tenosinovitis de d'extensors, vessament a l'articulació ràdio-carpiana, senyal Doppler positiva, sinovitis a l'articulació ràdio-carpiana, vessament a articulacions metacarp-falàngiques, vessament a articulacions interfalàngiques proximals, tenosinovitis de flexors. Aquestes alteracions s'associen a la presència de major activitat lúpica, produint una pitjor percepció de la qualitat de vida en el seu domini físic, però no en el mental, i produint una tendència a presentar major discapacitat.This Doctoral Thesis I have completed, I assessed several musculoskeletal manifestations that patients with Systemic Lupus Erythematosus patients from a metropolitan and Mediterranean region often complain. I studied two kind of patients, those with widespread musculoskeletal pain and those with hand and wrist inflammatory arthralgia. Both types of patients did not show inflammatory signs at physical exam. In the study of patients with widespread pain (fibromyalgia-like symptoms) I aimed the following objectives: to establish fibromyalgia, anxiety and depression prevalence; to assess the relationship between them; to demonstrate the absence of lupus activity in these patients and to assess the associated quality of life and disability. In the study of the inflammatory hand and wrist arthralgia I aimed the following objectives: to establish its relationship with the presence of ultrasound abnormalities; to describe these abnormalities; to demonstrate its association to lupus activity, and to assess the associated quality of life and disability. The methodology used was similar in both projects. I studied a well defined and controlled Systemic Lupus Erythematosus patient's cohort, and I defined inclusion criteria based on the symptoms aimed to evaluate. All participants were included consecutively after careful clinical interrogatory and physical exam. Patients and I fulfilled several activity, quality of life, disability, and psychiatric disorders questionnaires. They also received routine blood tests assessing main activity markers, and, in the second project, they were assessed by joint ultrasound at both hands. All data were registered and analysed after the cross-sectional intervention, through 2005-2009. The first work also compared data with lupus patients without fibromyalgia, and the second work compared data with lupus patients without hand and wrist arthralgia. A total of 84 patients were assessed in the study of widespread pain, and 58 were included in the study of hand and wrist arthralgia. Results were published in two different original articles in two scientific Rheumatology journals each. Conclusions: Patients with Systemic Lupus Erythematosus from a metropolitan and Mediterranean area showed a prevalence of 35.7% of both fibromyalgia and anxiety and 19% of depression. An association between the presence of fibromyalgia and psychiatric disorders was observed. No relationship to lupus disease activity was observed. Patients with fibromyalgia showed both mental and physical poorer quality of life. In patients with Systemic Lupus Erythematosus from a metropolitan and Mediterranean area a relationship between the presence of inflammatory hand and wrist arthralgia and the presence of ultrasound abnormalities was observed in up to 71.4%. The main ultrasound abnormalities observed were digital extensorum tenosynovitis, radio-carpal joint effusion, positive Doppler signal, radio-carpal joint synovitis, proximal interphalangeal joints effusion and digital flexorum tenosynovitis. These ultrasound abnormalities were associated to the presence of higher lupus activity, poorer physical quality of life (not mental) and a trend to higher disability

Bone mineral density and vitamin D status in systemic lupus erythematosus (SLE): A systematic review

Despite the improvement in the quality of life of patients with SLE due to scientific and technological advances, SLE remains a disease that over the years may produce irreversible damage to patients. Osteoporosis and secondary bone fractures are two of the major causes of irreparable injury in patients with SLE. Vitamin D insufficiency may play a vital role both in reduced bone mineral density (BMD) and in the appearance of fractures, although its mechanisms of action are still unclear. We performed a systematic review of the literature in order to determine the prevalence and predictors of reduced vitamin D plasma levels, bone loss and the presence of fractures in SLE patients. Our review encompassed all English-language publications using Medline and EMBase electronic databases from their inception (1966 and 1980, respectively) to December 2016. We included all intervention studies and observational studies in which vitamin D plasma levels, BMD and bone loss were measured and applied to patients with SLE. Previous studies suggested an increase in bone loss and fracture in patients with SLE compared with general population and although there is a high prevalence of vitamin D insufficiency in the general population, previous studies had demonstrated lower vitamin D levels in patients with SLE compared to age-matched controls. The etiology of reduced bone mass and reduced vitamin D plasma levels in SLE is multifactorial and includes a variety of intrinsic factors related to the disease itself and treatment side effects. SLE patients are at risk for developing these two comorbidities (reduced vitamin D plasma levels and low BMD) and it is therefore essential to study, monitor, prevent and treat bone metabolism disorders in SLE patient

Challenges of diagnosing cognitive dysfunction with neuropsychiatric systemic lupus erythematosus in childhood

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