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Annals of the Rheumatic Diseases | 2018
J. Ramírez García; A. Cuervo; Maria M. Alsina; R. Celis; V. Ruíz-Esquide; R. Castellanos; Mirtha Hernández; R. Sanmartí; Juan D. Cañete
Background Early diagnosis in psoriatic arthritis (PsA) is mandatory in order to initiate early therapy and prevent disability. Around 20% of patients with Psoriasis (PsO) routinely visited in Dermatology departments have PsA previously undiagnosed. Objectives The aim of this study is to evaluate the presence of inflammation by clinical examination and ultrasound in joints and enthesis of patients with PsO without musculoskeletal symptoms. Methods Patients with PsO under topic or PUVA therapy without musculoskeletal symptoms were referred to our Arhritis Unit. Clinical and demographic data were collected. The patients were evaluated for Body Surface Area (BSA), Swollen Joint Count (SJC) (66 joints), Tender Joint Count (TJC) (68 joints) and enthesis (MASES). Psoriatic Arthritis Impact of Disease tool questionnaire (PsAID) and Psoriasis Epidemiology Screening tool questionnaire (PEST) were used to assess the impact of the disease. A comprehensive ultrasound evaluation of 46 joints and 12 enthesis was made (ESAOTE MylabTwice, 12–18 Mhz probe). Enthesis score was calculated using the Madrid Sonographic Enthesis Index (MASEI) and a total score for synovitis (synovial hypertrophy and Power Doppler) was also calculated. Results 42 patients were included. 20 patients were female (48%), mean age (SD) was 48.3 y (14.6) and disease duration was 17.9 y (15.9). Mean BMI was 24.6 (5.2) and BSA 5 (8.7). 13 out of 42 (31%) had severe PsO (systemic treatment or BSA >10% at any time of evolution). 4 patients (9.5%) had Power Doppler signal and 2 (4.8%) fulfilled criteria for ultrasound-defined active synovitis (SH ≥2 + PD) despite no signs or symptoms of musculoskeletal disease. However, although structural alterations such as calcifications and enthesophytes were frequent, no PD was found at any enthesis. In the univariate analysis, higher BMI (p=0.013), weight (p=0.010), waist (p=0.033) and hip (p=0.014) circumferences were significantly associated with severe PsO. In the same way, CRP serum levels were also significantly higher in patients with severe PsO (p=0.027). A strong trend was found between higher MASEI scores and onycopathy (p=0.09). pan> Conclusions Patients with PsO under topic or PUVA therapy without musculoskeletal sympoms have a low prevalence of findings in the joints and enthesis ultrasound evaluation. Of note, 9.5% of PsO patients had subclinical synovitis defined as PD. No changes in those finding were found in a short follow-up (6 months) in these patients. A higher number of patients would be necessary to have strong results. These patients will be followed in order to confirm if they develop Psoriatic Arthritis. Acknowledgements This work was partially financed by Pfizer-Spain Disclosure of Interest None declared
Annals of the Rheumatic Diseases | 2016
A. Cuervo; Julio Ramírez; V. Ruiz-Esquide; Raquel Celis; Mirtha Hernández; J. Inciarte-Mundo; Raimon Sanmartí; Juan D. Cañete
Background Definitive biomarkers have not been identified to predict flares in patients with RA in clinical remission. Objectives To determine clinical, serological and ultrasonografic variables predicting disease relapse at 12 months of follow-up in a cohort of RA patients in clinical remission. Methods We included consecutively RA patients in clinical remission defined as DAS28-ESR <2.6 for >6months evaluated by two independent rheumatologist from our Arthritis Clinic. Complete clinical and biological assessment, determination of serum levels of angiogenic and proinflamatory cytokines, and ultrasound scans of both hands were performed at baseline and after 12 months of follow-up. Risk factors odds ratio (OR) related with 12 months flare were adjusted with multivariate logistic models. Results Sixty patients with RA in remission were included; 78.3% were female. Median age was 53 years (range: 31–74), weight was 67 kg (47–108). Disease and remission mean duration were 111.9 ± 86.4 and 37 months, respectively. 71% of patients were RF positive and 81% were ACPA positive. Patients taking low-dose prednisone, csDMARDs and bDMARDs were 16 (26%), 47 (78%) and 28 (46.7%), respectively. At baseline, 66% had power-doppler (PD) signal and 48% also had synovial hyperplasia grade ≥2, so fulfilling the criteria previously defined of ultrasound defined active sinovitis (UdAS). Twenty-six (43%) patients had disease flare during the follow-up. In the univariate analysis, disease flares were more frequent in patients with PD signal (p=0.056) or UdAS (p=0.117), and significantly less frequent in patients with mild-moderate intake of alcohol. However, in the multivariate analysis, only higher ESR levels (OR: 1.1, 95%CI: 1–1.1), higher weight (OR: 3.1, 95%CI: 1.4–7) and low-dose prednisone treatment (OR: 1.8, 95%CI: 1.2–2.8) were independent risk factors at baseline for disease flares. This model has a sensitivity of 76.9% (95%CI: 56.4–91), a specificity of 76.5% (95%CI: 58.8–89.3), a predictive positive value of 71.40% (95%CI: 52.4–88.4), a predictive negative value of 81.3% (95%CI: 62.7–91.7) and a good predictive power (ROC: 0.849, IC 95%: 74.4–95.4%). We did not find differences between angiogenic or proinflammatory cytokine serum levels and not differences in RAMRIS between patients relapsing or maintaining the remission at baseline. Conclusions This prospective study suggests that higher ESR levels, higher weight and low-dose prednisone treatment are relevant independent risk factors for development of disease flares in patients with RA in clinical remission. However, imaging data (Ultrasound or MRI) or angiogenic/cytokine serum levels were no predictors of flare in this study. Disclosure of Interest None declared
Annals of the Rheumatic Diseases | 2016
J. Inciarte-Mundo; Mirtha Hernández; V. Ruiz-Esquide; Julio Ramírez; A. Cuervo; S. Cabrera-Villalba; Mariona Pascal; Jordi Yagüe; Juan D. Cañete; Raimon Sanmartí
Background Calprotectin and TNF antagonist (TNFa) trough serum levels are associated with disease activity. Objectives To determine if calprotectin serum levels or drug trough serum levels predict relapse in RA and PsA patients with low levels of disease activity during TNFa therapy. Methods Prospective 1-year follow-up, single center study (INMUNOREMAR cohort). RA (ACR 1987) and PsA (CASPAR) patients in clinical remission (CR) (DAS28-ESR <2.6) or low disease activity (LDA) (DAS28-ESR <3.2) in ≥2 consecutive visits treated with adalimumab (ADA), etanercept (ETN) or infliximab (IFX) for ≥3 months were included. Demographic data, disease duration, time to initiate csDMARD and bDMARD, time to achieve remission, remission duration, autoantibody status, radiological data, concomitant csDMARD therapy, dose and duration of biological therapy were collected. Clinical and laboratory assessment was made every 4 months and at the time of flare. Calprotectin serum levels (ELISA Kit Calpro AS®) and TNFa trough serum levels (ELISA Kit Promonitor®, Progenika) were determined. Disease flare was defined as DAS28-ESR>3.2 and increase in ΔDAS28-ESR >0.6. Univariate and multivariate regression models were used to identify predictors of disease flare. Results 103 patients (47RA, 56PsA) were included. Mean Age 57 (30–81) years. 78 (75.8%) had CR and 25 (24.2%) LDA. Mean CR/LDA duration was 58 (4–163) months. 36 patients had received treatment with ADA, 50ETN, and 17IFX. Mean biologic treatment duration 61 (7–166) months. 47.4% patients were on monotherapy, 47% on reduced dose, and 17.9% received steroids. 84 patients (91%) remained in CR/LDA for 12 months, and 12 patients (13%; 8 RA, 4 PsA) experienced flares. Patients with flares had a longer time to achieve CR/LDA [CR/LDA (n=81) 3.1 (1–6) months vs. Flare (n=12) 20 (5–31) months, p<0.001], a shorter CR/LDA duration [CR/LDA (n=81) 59 (5–163) months vs. Flare (n=12) 25 (3–134) months, p=0.031], higher calprotectin levels [CR/LDA (n=81) 1.4 (0.6–3.7) μg/mL vs. Flare (n=12) 6 (4.5–7.9) μg/mL, p<0.001], and lower drug trough serum levels [CR/LDA (n=83) 2.6 (0.6–12) μg/mL vs. Flare (n=12) 0.6 (1–1.2) μg/mL; p<0.001], even when analyzed by biologic [ADA CR/LDA (n=30) 7 (0.2–12) μg/mL vs. Flare (n=4) 0.5 (0.4–1) μg/mL; p=0.003; ETN CR/LDA (n=44) 1.5 (0.7–4.7) μg/mL vs. Flare (n=5) 0.8 (0.9–1.2)μg/mL; p=0.039; IFX CR/LDA (n=14) 3.1 (0.5–7.7) μg/mL vs. Flare (n=3) 0.1 (0–1) μg/mL; p=0.021] at baseline. According to the cut-off developed by our group [1], patients with flares had sub-therapeutic baseline drug serum trough levels [CR/LDA (n=22) 26% vs. Flare (n=12) 100%, p<0.001]. Baseline TNFi trough serum levels [hazard ratio (HR) = 0.47], steroid treatment (HR=3.21), time to CR/LDA (HR=1.17), and baseline calprotectin levels (HR=2.38) significantly predicted flare in the univariate analysis but only baseline calprotectin levels significantly predicted flare in the multivariate analysis [HR=2.74 (1.74–4.31); p<0.0001]. Conclusions Calprotectin and TNF trough serum levels are promising biomarkers to predict flare in RA and PsA patients with low disease activity during anti-TNF treatment. References Sanmarti et al. Ann Rheum Dis. 2015 Aug;74(8):e42. Disclosure of Interest J. Inciarte-Mundo Grant/research support from: Hospital Clinic de Barcelona (Premi E. Letang 2013); Catalan Society of Rheumatology (Research Grant 2013), M. Hernández: None declared, V. Ruiz-Esquide: None declared, J. Ramírez: None declared, A. Cuervo: None declared, S. Cabrera-Villalba: None declared, M. Pascal: None declared, J. Yagüe: None declared, J. Cañete: None declared, R. Sanmarti Grant/research support from: This Study was supported by an Investigator Initiated Research (IIR) from Pfizer (WS2392358)
Annals of the Rheumatic Diseases | 2016
Julio Ramírez; José Antonio Narváez; V. Ruiz-Esquide; J. Hernández; Raquel Celis; A. Cuervo; Mirtha Hernández; J. Inciarte-Mundo; Raimon Sanmartí; Juan D. Cañete
Background A high proportion of patients with rheumatoid arthritis (RA) in clinical remission (CR) present subclinical synovitis when evaluated by sonography. Most prospective studies on baseline biomarkers of radiographic progression in this patients not include immunological biomarkers that could be of interest to better identify the residual inflammatory activity. Objectives To determine clinical, serological and ultrasonografic variables predicting progression of structural damage as evaluated by MRI at 12 months (mo.) of follow-up in a cohort of RA patients in CR. Methods We included 42 RA patients in CR defined as DAS28-ESR<2.6 for >6 mo. Complete clinical and biological assessment, ultrasonography of two hands and MRI of dominant hand were performed at baseline and after 12 mo. We analyzed risk factors related with RAMRIS progression with multivariate lineal models. Results 42 patients were included (76.7% female). Mean age was 53.5 years, body mass index (BMI) 26.7 kg/m2. Disease and remission median duration were 94 and 37 mo. respectively. 73.8% RF[+] patients and 85.7% ACPA [+]. RAMRIS 10.3 and erosion (RAMRIS) 18.8. At baseline, 66.7% had power-doppler (PD) signal and 45.2% also had synovial hyperplasia grade ≥2, so fulfilling the criteria of previously defined ultrasound defined active synovitis (UdAS)1. The risk factors more related with RAMRIS progression at 12 mo. were baseline RAMRIS, BMI, disease duration, low-dose prednisone treatment, absence of csDMARDs treatment and presence of UdAS. Synovitis as defined by only PD positive signal was no associated to erosions. We excluded the baseline RAMRIS in the multivariate model because it was the strongest predictor factor. We observed that higher serum levels of calprotectin and ENA78 at baseline were significant predictors. Absence of csDMARD treatment, disease duration and the presence of UdAS also remained as independent predictive factors (Table 1).Table 1. Risk factors and prognostic biomarkers associated with a higher score at one year RAMRIS Risk factor Unadjusted Adjusted β (95% CI) p-value β (95% CI) p-value Baseline calprotectin levels r=0.195 0.216 4.6 (1.2–8) 0.009 Baseline log2(ENA78) levels r=0.342 0.027 5.7 (0.4–11.1) 0.037 Longer disease evolution 0.08 (0.003–0.15) 0.043 0.07 (0.01–0.13) 0.027 No treatment with DMARDs 19.9 (2.6–37.2) 0.026 18.6 (3.8–33.3) 0.015 UdAS 16.7 (3.1–30.3) 0.017 17.1 (6.1–28.2) 0.003 Predictive value of the model Model indexes R, R2 (R2 adjusted) 70%, 49%, (41.9%) Overall significance of the model <0.0001 Conclusions This prospective study confirms a high prevalence of UdAS in patients with RA in CR, which is an independent risk factor to develop structural damage progression at 12 months of follow-up. Baseline RAMRIS, BMI, disease duration, absence of csDMARDs therapy, UdAS, and baseline levels of calprotectin and ENA78, were independent predictors of RAMRIS progression. References Ramírez J, et al. Patients with rheumatoid arthritis in clinical remission and ultrasound-defined active synovitis exhibit higher disease activity and increased serum levels of angiogenic biomarkers. Arthritis Res Ther. 2014;16(1):R5 Disclosure of Interest None declared
Annals of the Rheumatic Diseases | 2015
J. Ramírez García; J. Inciarte-Mundo; A. Cuervo; V. Ruíz-Esquide; Mirtha Hernández; R. Sanmartí; Juan D. Cañete
Objectives To analyse clinical, serological and sonographic differences in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) on anti-TNF therapy. Methods Patients diagnosed with RA or PsA in clinical remission (DAS28-ESR<2.6) on anti-TNF therapy were included. Angiogenic and proinflammatory cytokines were determined by Multiplex ELISA and compared with the same measurement in two control cohorts: active RA patients (DAS28>3.2) and healthy people. Ultrasound scans of both hands were performed in all participants, with scoring of synovial hypertrophy (SH) (grades 0-3) and power Doppler (PD) signal (grades 0-3). Results 30 RA and 47 PsA patients in clinical remission, 22 clinically-active (DAS28-ESR>3.2) RA patients and 20 healthy controls were included. RA patients in clinical remission had significantly higher disease activity (2.01 and 1.74, mean DAS28-ESR for RA and PsA, respectively, p=0.006) and higher levels of both proinflammatory (IL6, TNF, IL17F, IL23 and IL33) and angiogenic cytokines (Angiogenin, ANGPTL4, CXCL16, ENA78, PIGF and SDF1) compared with PsA patients in clinical remission. No differences were found in these mediators between PsA and healthy controls, whereas in RA patients in clinical remission these mediators were more similar to clinically active RA. Globally, 31 patients had a PD signal and 12 had SH≥2 plus PD, meeting the criteria of ultrasound-defined active synovitis (UdAS)]. Only 1 PsA patient met UdAS criteria compared with 11 RA patients in clinical remission (p=0.0001). Patients with UdAS had significantly higher levels of IL-6, IL-20, PIGF and SDF1. More PsA patients were receiving low doses of biologics (63.8%), and more frequently as monotherapy (72.3%) compared with RA patients in clinical remission (26.6% and 20%, respectively). Conclusions Clinical remission is qualitatively different in RA and PsA receiving TNF antagonist therapy. PsA patients had significantly-lower serum levels of angiogenic and proinflammatory cytokines and less ultrasound synovitis than RA patients. A significantly-higher percentage of PsA patients were receiving low doses of biologics, mainly with monotherapy compared with RA patients in remission. Patients with chronic inflammatory polyarthritis in clinical remission with UdAS had higher serum levels of angiogenic/proinflammatory biomarkers, supporting the idea that this reflects true active synovitis. Disclosure of Interest None declared
Annals of the Rheumatic Diseases | 2015
V. Ruiz-Esquide; Pascal Zufferey; Jordi Yagüe; J. Berner; J. Inciarte-Mundo; A. González-Navarro; V. Hernández; Julio Ramírez; A. Cuervo; Juan D. Cañete; Raimon Sanmartí
Background Tocilizumab (TCZ) is a humanized anti-IL-6R monoclonal antibody approved for the treatment of active rheumatoid arthritis (RA). Response to treatment may depend on the dose and dose interval as well as on the achieved trough serum levels. Objectives To analyze serum trough levels of TCZ in two cohorts of RA patients on chronic treatment with TCZ and their relationship with disease activity and clinical remission. To establish a cut-off point of TCZ serum levels with high discriminative capacity for clinical remission state. Methods Cross-sectional study of two cohorts (Barcelona, Spain and Lausanne, Switzerland) including all RA patients on chronic treatment with IV TCZ. Demographic data, disease activity measured by DAS28, acute phase reactants, TCZ trough levels (detectable levels ≥1μg/ml) (LISA TRACKER Tocilizumab Theradiaag, France) and IL6 serum levels (ELISA) were analyzed. All samples were collected just before treatment infusion. TCZ levels were correlated with different clinical and serological parameters. Multivariate logistic regression was used to determine the variables associated with remission (DAS28≤2.6). Receiver operating characteristic (ROC) curve analysis was used to determine the discriminatory capacity of the area under the curve (AUC) of TCZ levels in predicting remission. Results 82 RA patients were included (40 Barcelona Cohort, 42 Lausanne Cohort) (90% were women, mean age 55.5±13 years, disease duration of 13.7±8 years, 60.3% anti-CCP+, 22.2% on monotherapy, 37.2% received low dose glucocorticoids and 26.8% were on reduced dose of TCZ). The mean DAS28 was of 2.5±1.1 and 44 patients (54.3%) were in remission. Swiss patients had a lower disease activity and were more frequently in remission, had less glucocorticoids use and were less frequently on a reduced dose. 25 patients (30.5%) had undetectable levels of TCZ (<1 μg/ml), and this was associated in both cohorts with significantly higher levels of CRP and lower levels of IL-6. DAS28 was higher in patients with undetectable levels of TCZ, but the difference was significant only in Swiss patients (Barcelona cohort DAS28 3.25±1.2 vs 2.82±0.9, Lausanne cohort DAS28 2.79±1.02 vs 1.75±0.9, p=0.017 in patients with undetectable and detectable trough levels of TCZ respectively). The proportion or patients on clinical remission or low disease activity was higher on the group of patients with detectable trough levels of TCZ. There were no differences between groups in the use of combination therapy with glucocorticoids or DMARDs. In the multivariate analysis, detectable levels of TCZ and glucocorticoids use were independently associated with clinical remission. The TCZ trough level with the greatest discriminative capacity for remission was 3.48 μg/ml (AUC 0.724; 95% CI: 0.607-0.840; p=0.001) with a sensitivity of 79.5% and a specificity of 67%. Conclusions Detectable levels of TCZ (≥1 μg/ml) in RA patients on chronic treatment with TCZ were associated with lower disease activity and, especially, with lower CRP levels in the unvaried analysis, and with clinical remission in the multivariate analysis. The cut-off point with the greatest discriminative capacity for clinical remission was of 3.48 μg/ml. Disclosure of Interest None declared
Annals of the Rheumatic Diseases | 2015
A. Cuervo; V. Rosario; J. Inciarte; Julio Ramírez; J. Arόstegui; Raimon Sanmartí; Juan D. Cañete
Background The MEFV gene encodes the pyrin protein, which regulates IL-1b and IL-18 production, two cytokines that participate in the innate immune response. Mutations in the MEFV gene are associated with familial Mediterranean fever (FMF), but our group identified these mutations in patients with intermittent hydrarthrosis (IH) and palindromic rheumatism (PR). (1, 2). Objectives To analyse the clinical usefulness of MEFV gene mutation analysis in patients with undifferentiated arthritis (UA). Methods Descriptive, retrospective study including patients with UA who underwent systematic screening for MEFV gene mutations, and were followed at the Rheumatology Department, Hospital Clínic, Barcelona, between 2000 to 2014. The following clinical and demographic data were collected; age, sex, age at onset of disease, disease duration, joint swelling characteristics: frequency, duration, number of joints involved (monoarthritis, oligoarthritis or polyarthritis), location pattern (upper or lower extremities); seropositivity (rheumatoid factor and/or ACPA), final diagnosis and clinical response to colchicine. Results Ninety five patients were included (68% female, mean age 39.9±14.7 years, follow up 8.5±6 years). MEFV gene mutational analysis was positive in 21 patients (22%) and negative in 74 (78%). In patients with mutations, the duration of arthritis was <7 days in 72% patients; 86% had intermittent arthritis, frequently oligoarticular (53%) and commonly affecting the lower extremities (48%). The final diagnosis was: FMF (29%), IH (14%), RA (10%), PR (10%), PsA (10%), Behçet (5%), self-limited arthralgia (10%) and undifferentiated oligoarthritis (5%). 29% patients were RF and/or ACPA positive. 71% patients were treated with colchicine, of whom 86% had a good response. In patients without mutations, the duration of arthritis was <7 days in 63% patients; 76% had intermittent arthritis, 39% oligoarthritis, and lower extremities were involved in only 28%. The final diagnosis was: RA (22%), PR (22%), Behçet (7%), undifferentiated oligoarthritis (7%) and FMF (3%). 31% patients were RF and/or ACPA positive. Two patients with a diagnosis of FMF had a negative mutational analysis and had a good response to colchicine. Conclusions MEFV gene mutational analysis may be useful in the differential diagnosis of patients with undifferentiated arthritis, especially those with <7 days of duration, intermittent flares and involvement of the lower extremities. However, due to the difficulty in carrying out mutational analysis and the relatively low percentage of patients with mutations (22%) observed in our cohort, we recommend starting with a therapeutic strategy with colchicine in suspected patients, with only patients with a good clinical response being analysed for the MEFV gene mutation. References Cañete JD, et al. Arthritis Rheum 2006;54:20:2334–2337. Cañete JD, et al. Arthritis Rheum. 2007;56:2784–2788. Disclosure of Interest None declared
Annals of the Rheumatic Diseases | 2015
J. Inciarte-Mundo; Mirtha Hernández; S. Cabrera-Villalba; V. Ruiz-Esquide; Julio Ramírez; A. Cuervo; Juan D. Cañete; Raimon Sanmartí
Background Dose reduction of biological therapy in patients with chronic arthritis (CA) with a good clinical response is a common pattern in clinical practice. However, most published studies are based on cross-sectional data in small groups of patients. Objectives To analyse the evolution of CA patients receiving low doses of biologics and to describe predictive factors associated with maintaining reduced doses of biological therapy. Methods Observational, longitudinal, prospective study that analysed the evolution of 153 patients treated with standard or reduced doses of biologics with a two-year follow up. Variables analysed were: age, sex, diagnosis and disease duration, previous treatment (sDMARD, bDMARD), current bDMARD and dosage, duration of biological treatment. In patients on reduced doses: concomitant therapy (sDMARD, steroids), ESR and CRP were collected. In rheumatoid arthritis (RA) patients, autoantibody status, erosions, and DAS-28 score were analysed. A logistic regression model was used to identify factors associated with maintaining the reduced dose after 2 years. The confidence interval of the area under the ROC curve was estimated by bootstrap technique to internally validate the predictive capacity of the model. Results 153 patients were included between June and November 2011: 82 RA, 29 ankylosing spondylitis (AS), 20 psoriatic arthritis (PsA) and 22 with other diagnoses: 70 patients (45.7%) were on reduced doses of biologics. This cohort was followed prospectively for 2 years. Of the 153 patients initially included, 142 remained on biologics at 2 years and 11 discontinued (6 on lower doses and 5 on standard doses: 3 due to adverse events (malignancies), 2 to pregnancies, 2 to prolonged remission, 1 to death and 3 lost to follow-up). After 2 years of follow-up, 56 patients remained on low-dose biological therapy (39.4%) and 8 (5.6%) required an increase in the dose to the standard regimen. By contrast, 19 patients receiving the standard dose were on reduced doses at two years. 75 (52.8%) patients were on a reduced dose after two years follow up. In patients (37 RA, 13 PsA) in whom the DAS-28 score was analysed (mean ± SD), 17.9% (8 AR, 2 PsA) had low disease activity (2.8±0.2) and 71.4% (29 AR 11, PsA) were in remission (1.9±0.5). Univariate analysis, showed that patients who remained on a reduced dose after 2 years had less use of concomitant steroids in 2011 [9% vs. 45% (p<0.0001)] and lower ESR [8±6 vs. 2.9±1.5 (p<0.0001)], CRP [0.1±0.2 vs. 0.3±1.1 (p<0.0001)], and DAS-28 [2.3±0.3 vs. 2.9±1.5 (p<0.0001)] in 2011. Multivariate analysis showed that lower use of concomitant steroids in 2011 in all patients [adjusted odds ratio (AOR) =0.15, 95% CI 0.05 to 0.52, p=0.0026] was independently associated with the maintenance of reduced doses. In RA patients, a lower DAS-28 score in 2011 was also a predictor of maintaining reduced doses [AOR =0.24, 95% CI 0.10 to 0.59, p=0.0018]. The area under the ROC curve was 85.5% [95% (74.2% -91.5%] Conclusions In our cohort, 87.5% of patients receiving reduced doses in 2011 remained on them after 2 years of follow up. Factors associated with the maintenance of a clinical response with reduced biological doses in the multivariate model were lower previous use of steroids and a lower DAS-28 score. Disclosure of Interest None declared
Annals of the Rheumatic Diseases | 2015
J. Inciarte-Mundo; Mirtha Hernández; V. Ruiz-Esquide; Julio Ramírez; A. Cuervo; J. Amaya; Mariona Pascal; Jordi Yagüe; Juan D. Cañete; Raimon Sanmartí
Background Calprotectin is a major S100 leucocyte protein, associated with disease activity in rheumatoid arthritis (RA) patients. Calprotectin is a potentially biomarker more sensitive of disease activity than conventional acute-phase reactans. Objectives To evaluate the performance of calprotectin serum levels in stratifying disease activity in RA patients treated with TNF inhibitors (TNFi) compared with acute phase reactants. Methods Cross-sectional study, including consecutive RA patients (ACR 1987 criteria) from our arthritis unit receiving etanercept, adalimumab or infliximab. DAS28, SDAI, CDAI, joint counts, ESR, CRP and calprotectin serum trough levels were measured. Associations between calprotectin, ESR and CRP and articular indices were analysed by correlation and linear regression. Results 87 patients were included; mean duration of biological treatment was 82±46 months. 47 patients were in remission/low disease activity (DAS28≤3.2), and 40 had moderate/high disease activity (DAS28>3.2). Serum calprotectin levels were higher in active patients than in those in remission/low disease activity (2.21±1μg/mL vs. 4.28±2μg/mL, p≤0.001). Calprotectin, CRP and ESR distinguished between patients in remission/low disease activity and those with moderate/high disease active disease, according to all indices assessed. Calprotectin levels were significantly-lower in patients in remission compared to those with low disease activity according to all articular indices analysed, whereas ESR discriminated between disease states only according to DAS28, and CRP only according to SDAI. Calprotectin, but not CRP or ESR, strongly correlated with all composite indices and the 28 SJC/TJC (all r coefficients over 0.50). In patients in remission/low disease activity, calprotectin but not CRP or ESR, distinguished between patients with no swollen joints and those with ≥1 swollen joints (1.95±1μg/mL vs. 3.07±1μg/mL, p=0.010). Adjusted analysis showed a significant association between serum calprotectin levels and DAS28 according to different covariates (combined therapy, reduced dose, use of glucocorticoids, disease duration, autoantibody status and erosive disease). Backward selection of variables did not substantially modify the association between calprotectin and DAS28. The accuracy analysis with “activity by DAS28≤3.2” as the reference variable showed an AUC of 0.846 (95% CI 0.763 to 0.930, p≤0.001) with a cut-off calprotectin value of ≥3.2. μg/mL. The cut-off had a sensitivity of 77.5% and a specificity of 81.9%. Table 1 DAS28-ESR CDAI SDAI Remission (n=30) Low disease activity (n=17) Remission (n=11 ) Low disease activity (n=35) Remission (n=13 ) Low disease activity (n=34) (DAS28-ESR ≤2.6) (DAS28-ESR >2.6–3.2) (CDAI ≤2.8) (CDAI >2.8–10) (SDAI ≤3.3) (SDAI >3.3–11) Calprotectin (μg/mL) 1.56±1 3.36±1* 1.51±1 2.43±1† 1.84±1 2.36±1† CRP (mg/dl) 0.25±0.3 0.34±0.4 0.10±0.1 0.34±0.3 0.12±0.1 0.34±0.3† ESR (mm/h) 11.80±6 21.24±10* 14.18±1 15.51±10 16.92±9 14.56±9* p<0.001; †p<0.05. Conclusions Calprotectin is an accurate biomarker of disease activity in RA patients receiving TNFi therapy and show a better correlation with all disease states, including remission and low disease activity, than acute phase reactants (ESR and CRP). Disclosure of Interest None declared
Annals of the Rheumatic Diseases | 2014
J. Ramírez García; J. Inciarte-Mundo; V. Ruíz-Esquide; S. Cabrera; R. Celis; A. Cuervo; C. Saura; Juan D. Cañete; R. Sanmartí
Objectives To analyse clinical and sonographic differences between patients with rheumatoid arthritis and psoriatic arthritis with clinical remission or low disease activity on anti-TNF therapy. Methods Subanalysis of the 12 months follow-up prospective study INMUNOREMAR. Patients diagnosed with rheumatoid arthritis or polyarticular psoriatic arthritis in clinical remission or low disease activity by DAS28 on anti-TNF therapy (etanercept, adalimumab or infliximab) were included. Clinical, epidemiological, demographic and serological data at baseline were analysed. Ultrasound scans of both knees and hands (wrists, metacarpophalangeal [MCP], proximal interphalangeal [PIP] flexor and extensor tendons of the hand) were made. We quantified synovial hypertrophy (grades 0-3) and power Doppler signal (grades 0-3) in all patients and a global synovitis score was calculated. Data at study entry are presented. Results 100 patients (46 RA and 54 PsA, mean age (SD) 58.2 (11.4) years, disease duration 15.9 (8.8) years) were included. 50 patients were on etanercept, 35 adalimumab and 15 infliximab. 51 patients (39 PsA) were on monotherapy and 46 (31 PsA) were on anti-TNF dose-reduction. 48 patients had power Doppler signal and 45 met criteria for ultrasound-active synovitis (synovial hypertrophy + Power Doppler signal). Patients with psoriatic arthritis had significantly-less disease activity (p=0.0001 for DAS28-VSG) and fewer sonographic findings (Table 1): only 14 patients with PsA met criteria for active synovitis (31 for RA, p=0.0001). Table 1. Study population: clinical and ultrasound characteristics RA (46) PsA(54) P Female (%) 37(80.4) 25(46.2) 0.0001 Age (SD) (years) 62.6(10.9) 54.5(10.5) 0.0001 Disease duration (SD) (years) 17.0 (9.7) 14.9(8.0) 0.240 DAS28-VSG (SD) 2.31(0.5) 1.88(0.5) 0.0001 Remission (%) 30 (65.2) 47 (87.0) 0.016 Treatment Etanercept (%) 24(52.1) 26(48.1) Adalimumab (%) 16(34.7) 19(35.1) Infliximab (%) 6(13) 9(16.6) Dose reduction (%) 15(32.6) 31(57.4) 0.016 Prednisone (%) 14(30.4) 1(1.8) 0.0001 SH+PD (%) 31(67.3) 14(25.9) 0.0001 SH2+PD (%) 18(39.1) 1(1.8) 0.0001 Ultrasound global score (SD) 9.5 (6.8) 6.8(5.6) 0.046 RA, Rheumatoid arthritis; PsA, Psoriatic arthritis; SH, Synovial hypertrophy; PD, Power Doppler; ACPA, Anticitrulline-protein antibody; SD, standard deviation. Conclusions Among patients with clinical remission or low disease activity and anti-TNF therapy, PsA patients had significantly less clinical and sonographic activity. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5519
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University of Texas Health Science Center at San Antonio
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