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  • 1
    In: Nature, Springer Science and Business Media LLC, Vol. 611, No. 7934 ( 2022-11-03), p. 115-123
    Abstract: Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry 1,2 . Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated ( P   〈  0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis 3 , and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN ) and variants (such as at GRK5 and NOS3 ). Using a three-pronged approach 4 , we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry 5 . Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 2
    In: Nature, Springer Science and Business Media LLC, Vol. 612, No. 7938 ( 2022-12-01), p. E7-E7
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    RVK:
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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    detail.hit.zdb_id: 1413423-8
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  • 3
    In: Revista Española de Cirugía Ortopédica y Traumatología, Elsevier BV, Vol. 65, No. 1 ( 2021-01), p. 54-62
    Type of Medium: Online Resource
    ISSN: 1888-4415
    Language: Spanish
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 4
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 1402.2-1403
    Abstract: Patients with inflammatory arthralgia (IA) are considered to be at increased risk for progression to RA. US has shown high sensitivity to detect synovitis compared with physical examination. Thus, US is recommended to identify subclinical synovitis in patients without clinical signs of inflammation. Objectives: The objective of our study is to determine the frequency and pattern of US detected inflammatory findings in patients with IA and investigate factors contributing to predict these findings. Methods: An US clinic is scheduled in an academic center running three days every week. A retrospective analysis of our US unit cohort during a period of 6 months was undertaken. Patients with IA and no previous diagnosis of inflammatory arthropathies were included for analysis. Inclusion criteria of IA definition included: severe symptoms presenting in the morning, duration of morning stiffness ≥60 min, symptoms predominantly located in MCP joints and abscense of clinically detected synovitis by the referral rheumatologist. The following routinely collected variables were included in the analysis: demographics, clinical features and laboratory tests. Patients underwent bilateral US examination in GS and PD mode of hands and/or feet according to the European League Against Rheumatism (EULAR) guidelines. The presence of synovitis, tenosynovitis and enthesitis was assessed on a semi quantitative scale (0–3) for Grey Scale(GS)/Power Doppler(PD) or using enthesitis OMERACT definition, respectively. Patients were stratified in two groups based on the presence of US inflammatory findings (synovitis, tenosynovitis or enthesitis with PD signal). First, differences between groups were tested using chi-squared and Student-t tests in the univariate analysis. Second, multivariate logistic regression models were employed to investigate the association between possible predictive factors of US detected inflammatory findings. Results: A total of 57 patients were included in the analysis. Mean age was 55.8±15.2 years, 41 (71.9%) were females, and mean symptoms duration was 11.4±10.4 months (Table 1). A total of 42 (73.7%) patients presented with a polyarticular arthralgia pattern. US inflammatory findings were present in 20 (35.1%) patients (26.3% PD synovitis, 21.1% PD tenosynovitis and 3.5% PD enthesitis). Hands were most commonly involved with PD synovitis at wrists in 19.3% and at MCP in 12.3% of patients (Table 2). For PD tenosynovitis, the flexor MCP 2-5 (5.3%) and compartment IV tenosynovitis (1.8 %) were the most frequent affected locations. Only two patients had PD enthesitis at feet and 6 (10.5%) had erosions in hands or feet at baseline examination. In the univariate analysis, the higher ESR values and the shorter time from symptoms onset were significantly associated with US detected inflammatory findings (p=0.044 and 0.049, respectively). In the multivariate analysis, only ESR values (OR=1,04; 95%CI 1,002-1,078), remained significantly associated with the presence of US inflammatory findings (Table 3). Table 3. Independent predictors of US detected inflammatory findings p Odds ratio 95% C.I. Lower Upper ESR (mm/h) 0.039 1.04 1.002 1.078 Time (months) from symptoms onset 0.1 0.924 0.841 1.015 Conclusion: PD US inflammatory findings are found in 1 over 3 patients with IA being PD synovitis the most common finding, specially at the wrists and MCP joints. Higher ESR values were significantly associated with the presence of US inflammatory findings. Our data highlights how the use of PD US may be useful to detect subclinical synovitis in patients with IA. Disclosure of Interests: Katerine López Gloria: None declared, Isabel Castrejon: None declared, Laura Trives Folguera Speakers bureau: ROCHE, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi, Belén Serrano Benavente: None declared, Julia Martínez-Barrio Consultant of: UCB Pharma, Javier Rivera: None declared, Carlos Gonzalez Consultant of: Gilead, Janssen, Novartis,, Speakers bureau: Abbvie, Celgene, Gilead, Janssen, Novartis, Pfizer, Roche, Indalecio Monteagudo: None declared, Jose-Maria Alvaro-Gracia Grant/research support from: Abbvie, Elli-Lilly, MSD, Novartis, Pfizer, Consultant of: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB, Paid instructor for: Elli-Lilly, Pfizer, Roche, Speakers bureau: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, Gedeon Richter, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB, Juan Molina Collada: None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
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    Language: English
    Publisher: BMJ
    Publication Date: 2020
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  • 5
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    BMJ ; 2020
    In:  Annals of the Rheumatic Diseases Vol. 79, No. Suppl 1 ( 2020-06), p. 1795.1-1797
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 1795.1-1797
    Abstract: Juvenile idiopathic arthritis (JIA) comprises a group of inflammatory diseases that frequently requires systemic treatments. There are some studies that evaluate the systemic drug survival in adults with JIA; but there is scarce data about the drug survival in paediatric population. Objectives: Our main objective was to study the drug survival of biologic therapies and synthetic DMARD in a monocentric cohort and the related factors influencing on it. Methods: Patients with JIA visited in the last 12 years were included. We carried out a retrospective, longitudinal study and collected data on treatment (start date, tapering and stop the treatment date; causes of finish and combined treatment or not). We also collected demographic data with date of birth, sex, symptoms onset data and JIA subcategory. We studied time to relapse since the drug suspension. The drug survival for each kind of treatment was analyzed with Kapplan-Meier curves. Results: We included 158 patients with JIA. Demographic data are shown in table 1. One hundred and thirty (82.3%) patients started methotrexate (MTX) with a half-life of 34.8 months; 79 (51.5%) patients started biologic therapy with half-life of 29 months and 14 (17.7%) patients started a second biologic with a half-life of 5 months. Time to first tapering of MTX was 12 months, for the first biologic was 10.5 months and for the second biologic was of 15 months. The main cause of suspension was remission for each group. Treatment according to different JIA subcategories is shown in table 2. In 45 patients (28.5%) systemic treatment was stopped and 11 (24.4%) had a disease flare in a mean time of 36 months. Taking into account only patients who flared, the mean time was 15.6 months. Table 1. Overview of patients with BSLE. BMZ: basal membrane zone MTP: methylprednisolone DDS: dapsone Table 1. Demographic features of the patients. Total (n:158) Sex (female) 96 (60,76%) Starting age (median y RI) 4,9 (2,6-9,8) AAN positives 91 (57,6%) JIA oligo persistent 66 (41,77%) JIA oligo extended 16 (10,13%) JIA enthesitis 14 (8,86%) JIA psoriasic 9 (5,7%) JIA systemic 18 (11,39%) JIA poli FR- 29 (18,35%) JIA poli FR+ 4 (2,53%) JIA undifferentiated 2 (1,27%) Table 2. All diseases that are diagnosed in patients during the follow-up period. Group 1 (Systemic JIA n=18 (%) Group 2 (Oligoarticular JIA n=82 (%) Group 3 (Poliarticular JIA n=33 (%) Group 4 (Juvenil SpA n=23 (%) Synthetic DMARD (n:130) 9 (50%) 71 (86,6%) 33 (100%) 17 (74%) Biologic Therapy (n:79) 6 (33,3%) 34 (41,46%) 22 (75%) 17 (74%) No systemic treatment (n:21) 7 (38,9%) 10 (12,2%) 0 4 (17.4%) Fig 1. Histology and DIF of BSLE H-E a and b : subepidermal blisters c and d : abundant neutrophils are observed e : DIF full house linear pattern Fig 2. skin lesions of BSLE a : tense serous blisters, scars and erosions b : purpuric macules in palms c : blisters in groin d-g : blisters and hypopigmented scars Conclusion: The drug survival for systemic therapies in children with JIA is more than 2 years, without significant differences between synthetic DMARDs and biologics. Remission is the main cause for ending treatment. Biologic drug survival was significantly shorter between systemic JIA and the other subcategories. Only one fourth of patients had a flared after stopping the systemic treatment. Disclosure of Interests: Laura Trives Folguera Speakers bureau: ROCHE, Indalecio Monteagudo: None declared, Belén Serrano Benavente: None declared, Liz R. Caballero Motta: None declared, Ana Melissa Anzola: None declared, Katerine López Gloria: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
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    Language: English
    Publisher: BMJ
    Publication Date: 2020
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  • 6
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 1465.2-1465
    Abstract: Metotrexate (MTX) is usually the first line therapy for Rheumatoid Arthritis (RA) because of its favorable efficacy-toxicity ratio. However the exact mechanism and treatment response time in both a clinical and ultrasonographic setting are still uncertain. Objectives: To describe the clinical and ultrasound response to MTX during the first 6 months of treatment in early RA patients who started subcutaneous methotrexate as the first disease-modifying drug (DMARD). Methods: Ongoing prospective cohort of patients with early RA (ACR-EULAR 2010 criteria), over 18 years and starting MTX-SC. Patients had a clinical and ultrasonographic evaluation at baseline, 1, 3 and 6 months. We collected demographic data, C-reactive protein [CRP], erythrocyte sedimentation rate [ESR] , rheumatoid factor [FR], anti-citrullinated protein antibody [ACPA] ), inflammatory activity indexes (DAS28esr and DAS28crp) and EULAR’s response to treatment (delta value of -1.2 in DAS28 scores). Joints explored with ultrasound were elbows and wrists (radio-carpal and inter-carpal joint) counted as a single joint, 1st-5th metacarpophalangeal (MCF), proximal interphalangeal (IFP), knees, tibio-talar and subtalar joints and 2nd-5th metatarsophalangeal (MTF) joints. Bone erosions were evaluated in 2nd and 5th MCF, styloid, distal ulna and 5th MTF. Synovitis was graduated semi-quantitatively from 0 to 3 (OMERACT) and calculated on B mode and Doppler. Results: 35 patients were included (mean age 61.2 years, 65.7% women) with a median of 0.8 (+/-8) months delay to diagnosis. 34 patients (97.1%) started 15mg MTX-SC/weekly. A higher DAS28esr was found in baseline data for the group that had a response by month 1 (DAS28esr baseline 5.5 vs 4.2 p=0.01), no other significant differences were found. During the first month, a significant response was achieved in 13 (41%) patients and remission in 11 (35%) (Table 1). 17 patients have 6 th month data. 11 (64.7%) have achieved EULAR response compared to baseline(P=0.0005) out of which 7 (54.5%) had already reached it by month 1. A difference in MTX dose (month1 14.8 vs month6 17.1 p=0.003) was found between month 1 and 6, with no differences in disease activity. In the ultrasonographic baseline data; 8 patients (22.9%) had erosions, with a mean of 2,75 erosions/patient (22 of the 280 locations). During the follow up the global rating lowered, with no differences in B mode but significant differences in Doppler at the 6 month mark (Table 2). As of this report, 10 patients (28.5%) had stopped MTX treatment due to lack on response or adverse effects and 8 (22.9%) are waiting 6 th month evaluation. Table 2. Ultrasound synovitis global rating. Baseline Month 1 P Value EULAR response 0 13 (41) 0.00005 MTX Dose mg (SD) 14.8 (+/-0.8) 14.8 (+/-1.6) 1 Prednisone Dose mg(SD) 5.9 (+/-6.5) 2.9 (+/-3) 0.02 DAS28crp (SD) 4.3 (+/-1.5) 3,4 (+/-1.4) 0.02 DAS28esr (SD) (4.8 (+/-1.5) 3.7 (+/-1.4) 0.006 Remission (DAS28 〈 1.2) 3(9.6) 11(35.5) 0.04 Table 1. Baseline characteristics of the patients with RA (n=102). Baseline N=35 1 month N=31 3 months N=25 6 months N=17 B Mode: Median (interquartile range) 8 (3.5-12) 8 (3-12.5) 6 (4-11) 5 (2-11) p 0,16 Doppler Mode : Median (interquartile range) 2 (0.5-6) 2 (0-6) 2 (0-6) 0 (0-2) p 0,005 Conclusion: In this cohort half of the patients that responded to treatment had achieved this by month 1. A higher baseline inflammatory profile was related to the response. Little difference is found between month 1 and 6 on clinical data, however ultrasonographic results suggest that at least 6 months are needed for Doppler improvement. Perhaps MTX has a faster effect over joint pain and lowers DAS28 scores requiring longer to completely suppress inflammatory activity. References: [1]Braun, J. et al. Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis. Arthritis Rheum 2008 Disclosure of Interests: Liz R. Caballero Motta: None declared, Ana Melissa Anzola Alfaro: None declared, Luis A Torrens Cid: None declared, Christian Y Soleto: None declared, Belén Serrano Benavente: None declared, Iustina Janta: None declared, Juan Molina Collada: None declared, Carlos Gonzalez Consultant of: Gilead, Janssen, Novartis,, Speakers bureau: Abbvie, Celgene, Gilead, Janssen, Novartis, Pfizer, Roche, Indalecio Monteagudo: None declared, Jose Maria Alvaro Gracia: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
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    Language: English
    Publisher: BMJ
    Publication Date: 2020
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  • 7
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 81, No. Suppl 1 ( 2022-06), p. 1423-1424
    Abstract: Ultrasound (US) is a valid imaging tool to detect signs of giant cell arteritis (GCA). Although the halo sign has always been considered the most useful finding for GCA diagnosis, modern high frequency transducers are able to precisely measure the intima-media thickness (IMT) of cranial and extracranial arteries. However, data on optimal cut-off values for IMT to differentiate patients and controls in clinical practice are limited. Objectives To determine the optimal cut-off value for IMT of cranial and extracranial arteries in patients with suspected GCA. Methods This is a retrospective observational study of patients referred to our US fast-track clinic with suspected GCA. All patients underwent bilateral US examination of the cranial and extracranial (carotid, subclavian and axillary) arteries within 24 hours per protocol. The exam was performed using an EsaoteMyLab8 with a 12-18 MHz frequency transducer for cranial arteries and an 8-14 frequency transducer for extracranial arteries. The IMT was measured in gray scale mode and the presence of a non-compressible halo sign was checked in all arteries. The gold standard for GCA diagnosis was clinical confirmation by the referring rheumatologist after 6 months follow-up. Mean IMT values of each artery were compared between patients with and without GCA by independent samples T-test. Receiver operating characteristics analysis was performed and the Youden index was used to determine the optimal cut-off value for IMT of each artery. Results Of the 157 patients with suspected GCA (67.5% female, mean age 73.7 years) referred to the fast-track clinic, 47 (29.9%) had GCA clinical confirmation after 6 months. 41 (87.2%) patients with GCA had positive US findings (61.7% had cranial involvement, 44.7% extracranial involvement and 19.1% a mixed pattern of cranial and extracranial arteries). The following IMT cut-off values showed the highest diagnostic accuracy: 0.44mm for the common superficial temporal artery; 0.34 mm for the frontal branch; 0.36 mm for the parietal branch; 1.1 mm for the carotid artery: 1 mm for the subclavian and axillary arteries. The area under the ROC curve of the IMT for a clinical diagnosis of GCA was 0.984 (95% CI 0.959 - 1) for common superficial temporal artery, 0.989 (95% CI 0.976 -1) for frontal branch, 0.991 (95% CI 0.980 - 1) for parietal branch, 0.977 (95% CI 0.961 – 0.993) for carotid, 0.99 (95% CI 0.979 - 1) for subclavian and 0.996 (95% CI 0.991 -1) for axillary arteries (Table 1). Table 1. Optimal IMT cut-off values for cranial and extracranial arteries Artery Side Patients without GCA Patients with GCA Cut-off (mm) AUC (CI 95%) Sensitivity (%) Specificity (%) Common superficialtemporal artery mm, mean (SD) Right 0.33 (0.06) 0.68 (0.28) 0.43 0.997 (0.988 -1) 100 97.1 Left 0.35 (0.11) 0.57 (0.21) 0.45 0.966 (0.905 -1) 100 92.3 Both 0.34 (0.08) 0.63 (0.25) 0.44 0.984 (0.959 -1) 94.7 95.1 Frontal branch mm, mean (SD) Right 0.26 (0.05) 0.4 (0.18) 0.34 0.994 (0.983 -1) 100 97.1 Left 0.27 (0.05) 0.4 (0.18) 0.34 0.985 (0.962 -1) 100 96.1 Both 0.26 (0.05) 0.4 (0.18) 0.34 0.989 (0.976 -1) 100 96.6 Parietal branch mm, mean (SD) Right 0.27 (0.05) 0.43 (0.18) 0.36 0.994 (0.981 -1) 100 98.9 Left 0.27 (0.05) 0.41 (0.16) 0.36 0.987 (0.967 -1) 100 97.6 Both 0.27 (0.05) 0.42 (0.17) 0.36 0.991 (0.980 -1) 100 98.3 Carotid mm, mean (SD) Right 0.8 (0.17) 0.88 (0.29) 1 0.974 (0.949 – 0.999) 100 92.6 Left 0.82 (0.15) 1 (0.42) 1.2 0.982 (0.961 - 1) 90.9 96.2 Both 0.81 (0.16) 0.96 (0.36) 1.1 0.977 (0.961 – 0.993) 90 94 Subclavian mm, mean (SD) Right 0.74 (0.18) 0.99 (0.44) 1 0.987 (0.97 - 1) 100 93.4 Left 0.67 (0.17) 0.9 (0.35) 1.1 0.991 (0.975 - 1) 100 98.3 Both 0.7 (0.18) 0.94 (0.4) 1 0.99 (0.979 - 1) 100 96 Axillary mm, mean (SD) Right 0.69 (0.16) 0.99 (0.5) 1 0.992 (0.982 - 1) 100 96 Left 0.67 (0.17) 0.99(0.49) 1 0.998 (0.995 -1) 100 98.3 Both 0.68 (0.17) 0.99 (0.49) 1 0.996 (0.991 -1) 100 97.1 Conclusion Different IMT cut-off values for each artery are necessary to establish a correct US diagnosis of GCA. These proposed IMT cut-off values may help to improve the diagnostic accuracy of US in clinical practice. Disclosure of Interests None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
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    Language: English
    Publisher: BMJ
    Publication Date: 2022
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  • 8
    In: Leukemia, Springer Science and Business Media LLC, Vol. 35, No. 6 ( 2021-06), p. 1571-1585
    Type of Medium: Online Resource
    ISSN: 0887-6924 , 1476-5551
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2008023-2
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  • 9
    In: Haematologica, Ferrata Storti Foundation (Haematologica), ( 2023-05-18)
    Abstract: Treatment options for patients with secondary and myeloid related changes acute myeloid leukemia (sAML and AML-MRC) aged 60-75 years old are scarce and unsuitable. A pivotal trial showed that CPX-351 improved complete remission with/without incomplete recovery (CR/CRi) and overall survival (OS) as compared with standard 3+7. We retrospectively analyze outcomes of 765 patients with sAML and AML-MRC aged 60-75 years treated with intensive chemotherapy (IC), reported to the PETHEMA registry before CPX-351 became available. The CR/CRi rate was 48%, median OS 7.6 months (CI95%, 6.7-8.5) and event-free survival (EFS) 2.7 months (CI95%, 2-3.3), without differences between IC regimens and AML type. Multivariate analyses identified age ≥70 years, ECOG≥1 as independent adverse prognostic factors for CR/CRi and OS, while favorable/intermediate cytogenetic risk and NPM1 were favorable prognostic factors. Patients receiving allogeneic stem cell transplant (HSCT), auto-HSCT, and those who completed more consolidation cycles showed improved OS. This large study suggests that classical intensive chemotherapy could lead to similar CR/CRi rates with slightly shorter median OS than CPX-351.
    Type of Medium: Online Resource
    ISSN: 1592-8721 , 0390-6078
    Language: Unknown
    Publisher: Ferrata Storti Foundation (Haematologica)
    Publication Date: 2023
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    detail.hit.zdb_id: 2030158-3
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  • 10
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 1478.2-1479
    Abstract: Tofacitinib is an oral JAK 1 and 3 inhibitor for the treatment of moderate to severe active rheumatoid arthritis (RA) or psoriatic arthritis (PsA) in adults with inadequate response or intolerant to one or more conventional disease-modifying antirheumatic drugs (cDMARDs). Since its approval by the European Medicines Agency (EMA), there is limited data about its use in daily practice in Europe. Objectives: To describe rates and reasons for discontinuation of Tofacitinib in patients with RA and other inflammatory conditions Methods: We identified patients with a prescription for tofacitinib at our academic center from January 2017 to January 2020. Patients were treated according to their rheumatologist evaluation following standards of care. The following variables were retrospectively collected from the electronic medical chart: age, gender, diagnosis, date of treatment initiation, date and reasons for treatment discontinuation, the use of concomitant or previous cDMARDs and of biologics. A comparison between patients continuing and stopping tofacitinib was performed through chi 2 or t-test for qualitative and quantitative variables, respectively. Survival analysis was done by Kaplan-Meier method Results: Ninety patients receiving tofacitinib were identified, 81 with RA, 6 with PsA, 1 with Dermatomyositis, 1 with Sjögren´s and 1 with juvenile idiopathic arthritis. Table 1 shows the baseline characteristics. 84% percent patients were women and the mean (SD) age was 58.5 (14.2) years. 51% patients started tofacitinib in monotherapy. When used, methotrexate was the most frequent cDMARD (61.3%); 10% patients used tofacitinib as first line after cDMARD and the majority used it after 1 or 2 previous biologics (46.7%). Table 2. Clinical coutcome of patients who developed HZ at initiation of baricitinib All patients (n=90, 100%) Continue Tofacitinib (n=58; 64%) Not continue Tofacitinib (n=32; 35.5%) p-value Female (%) 76 (84.4) 48 (82.7) 28 (87.5) 0.55 Age (year) – mean (SD) 58.5 (14.2) 58 (12.9) 59.5 (16.5) 0.63 Diagnosis 0.66 Rheumatoid arthritis 81 (90) 52 (89.6) 29 (90.6) Psoriatic arthritis 6 (6.7) 4 (6.8) 2 (6.2) Other 3 (3.3) 2 (3.4) 1 (3.1) Treatment duration (months) – mean (SD) 10.6 (6.9) 11.9 (7.3) 8.2 (5.5) 0.02 Prednisone (mg) – mean (SD) 1.75 (3.2) 1.20 (2.5) 2.73 (4.1) 0.03 Monotherapy (%) 46 (51.1) 28 (48.2) 18 (56.2) 0.244 Concomitant csDMARDs (%) 44 (48.8) 30 (51.7) 14 (43.7) 0.62 Methotrexate (%) 27 (30) 17 (29.3) 10 (31.2) Leflunomide (%) 10 (11.1) 8 (13.7) 2 (6.2) Other (%) 7 (7.7) 5 (8.6) 2 (6.2) Prior biologic treatment 0.13 None (%) 9 (10) 6 (10.3) 3 (9.3) 1-2 (%) 42 (46.6) 28 (48.2) 14 (43.7) ≥3 (%) 39 (43.3) 24 (41.3) 15 (46.8) Survival rates when used as first or second line were 85% at 6 months and 70% at 12 months; when used as third line or further, 76% and 70%, respectively (graphic 1). Factors associated to tofacitinib discontinuation were treatment duration and baseline prednisone dose. In contrast concomitant csDMARD and number of previous biologics were not. Reasons for tofacitinib discontinuation were: lack/loss of efficacy 46.9%, adverse events 50% (including intolerance -22%- herpes zoster -16%-, other infections 12%) and others. Conclusion: Tofacitinib in our experience is mostly used in RA patients after biologic failure. Overall survival rate at 12 months was good regardless line of therapy. Adverse event rates were similar to other biologic treatments. Herpes zoster was the most common infectious AE. Graphic 1: References: [1]Wollenhaupt J, Lee EB, Curtis JR, et al. Safety and efficacy of tofacitinib for up to 9.5 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study. Arthritis Res Ther. 2019;21(1):89. Disclosure of Interests: Christian Y Soleto: None declared, Belén Serrano Benavente: None declared, Luis A Torrens Cid: None declared, Julia Martínez-Barrio Consultant of: UCB Pharma, Juan Molina Collada: None declared, Javier Rivera: None declared, Teresa González: None declared, Indalecio Monteagudo: None declared, Carlos Gonzalez Consultant of: Gilead, Janssen, Novartis,, Speakers bureau: Abbvie, Celgene, Gilead, Janssen, Novartis, Pfizer, Roche, Isabel Castrejon: None declared, Jose-Maria Alvaro-Gracia Grant/research support from: Abbvie, Elli-Lilly, MSD, Novartis, Pfizer, Consultant of: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB, Paid instructor for: Elli-Lilly, Pfizer, Roche, Speakers bureau: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, Gedeon Richter, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1481557-6
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