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1.
Artigo em Inglês | MEDLINE | ID: mdl-31722413

RESUMO

OBJECTIVE: In early RA, some patients exhibit rapid radiographic progression (RRP) after one year, associated with poor functional prognosis. Matrices predicting this risk have been proposed, lacking precision or inadequately calibrated. We developed a matrix to predict RRP with high precision and adequate calibration. METHODS: Post-hoc analysis by pooling individual data from cohorts (ESPOIR and Leuven cohorts) and clinical trials (ASPIRE, BeSt and SWEFOT trials). Adult DMARD-naïve patients with active early RA for which the first therapeutic strategy after inclusion was to prescribe methotrexate or leflunomide were included. A logistic regression model to predict RRP was built. The best model was selected by 10-fold stratified cross-validation by maximizing the Area Under the Curve. Calibration and discriminatory power of the model were checked. The probabilities of RRP for each combination of levels of baseline characteristics were estimated. RESULTS: 1306 patients were pooled. 20.6% exhibited RRP. Four predictors were retained: rheumatoid factor positivity, presence of at least one RA erosion on X-rays, CRP > 30mg/l, number of swollen joints. The matrix estimates RRP probability for 36 combinations of level of baseline characteristics with a greatly enhanced precision compared with previously published matrices (95% CI: from ± 0.02 minimum to ± 0.08 maximum) and model calibration is excellent (P = 0.79). CONCLUSION: A matrix proposing RRP probability with high precision and excellent calibration in early RA was built. Although the matrix has moderate sensitivity and specificity, it is easily usable and may help physicians and patients to make treatment decisions in daily clinical practice.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31628807

RESUMO

OBJECTIVE: Evaluating radiographic progression is a key component of the follow-up of patients with RA. Existing scores are ill-suited to everyday clinical practice. The objective here was to validate a new simplified radiographic score (SRS) for evaluating radiographic progression in patients with early arthritis. METHODS: Patients with arthritis of <6 months' duration were included in the large, prospective, nationwide, French ESPOIR cohort. Radiographs of the hands and feet were obtained at inclusion then 1 and 5 years later. The modified Sharp scores and SRS were determined by blinded readers. Interobserver reliability and intraobserver repeatability of each score, as well as agreement between the two scores, were assessed by computing the intraclass correlation coefficients. The rates of progression over the first year and the next 4 years were determined. RESULTS: The 506 patients with complete data for the first 5 years were included. At inclusion, the intraclass correlation coefficient between the two scores was good for erosions (0.715, P < 0.001), joint space narrowing (0.892, P < 0.001) and the total score (0.896, P < 0.001). Agreement between the two scores was also good for radiographic progression after 1 year (0.781, P < 0.001). The SRS had good positive and negative predictive values for slow and for rapid progression. SRS determination was less time consuming. CONCLUSION: The SRS is effective for monitoring radiographic progression in early arthritis and is easier to use and less time-consuming than the Sharp score. The usefulness of the SRS in clinical practice deserves further evaluation.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31526593

RESUMO

OBJECTIVE: The Flare Assessment in Rheumatoid Arthritis (FLARE-RA) questionnaire was devised for the detection of flares in patients with RA. We aimed to define construct validity and cut-off(s) for the FLARE-RA questionnaire. METHODS: This cross-sectional study included adult patients with prevalent RA (2010 ACR/EULAR criteria) attending outpatient rheumatology clinics in France (n = 138), Denmark (n = 253), USA (n = 75), and Argentina (n = 105). Flare occurrence over the past 3 months was assessed with the FLARE-RA questionnaire scoring from 0 (no flare) to 10 (maximum flare). The cut-offs for the FLARE-RA score were defined using the following anchor items obtained at the same encounter: (1) Patient report of flare; (2) DAS28-CRP > 3.2; (3) Change of anti-rheumatic treatment, based on the area under the receiver operating characteristic curve (AUC) and distance to (0,1). RESULTS: Four hundred seventy four patients with RA duration ≥2 years (mean age 58.6 years, 74.9% female) were included in the main analysis. The discrimination for the FLARE-RA cut-offs was acceptable-to-excellent: AUC for the global FLARE-RA score ranged from 0.71 to 0.92. The cut-offs for the FLARE-RA score were lower using "patient report of flare" than DAS28-CRP and "change of anti-rheumatic treatment". Proposed FLARE-RA cut-offs for clinical detection and change of anti-rheumatic treatment are 2 and 5, respectively, for patients with RA duration 2-5 years, and 2 and 3.5, respectively, for patients with RA duration >5 years. CONCLUSIONS: Proposed FLARE-RA cut-offs have acceptable discriminative capacity across the tested anchor items and are expected to aid in early recognition and timely management of RA flares.

7.
Ann Phys Rehabil Med ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31421275

RESUMO

BACKGROUND: Individuals with chronic low back pain (cLBP) may benefit from multimodal functional restoration programs (FRPs). OBJECTIVE: The aim of this study was to analyze characteristics of individuals with cLBP who were referred or not to an FRP. Because cLBP is a bio-psycho-social disorder, medical and social parameters were analysed. METHODS: This was an observational cross-sectional study performed in 2017 in 6 tertiary centres in France. Consecutive individuals with cLBP visiting a rheumatologist or physical medicine and rehabilitation physician were included. Individuals referred or not to an FRP were compared by demographic characteristics, duration of sick leave over the past year, self-reported physical activity>1h/week, pain (numeric rating scale 0-10), anxiety/depression (Hospital Anxiety and Depression Scale), disability (Oswestry Disability Index) and kinesiophobia (Tampa Kinesiophobia Scale). Univariate and multivariate logistic regression analyses were performed, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 147 individuals with cLBP. The mean (SD) age was 49 (12) years and 88 (60%) were women; 58 (38%) were referred to an FRP. On multivariate analysis, referral to an FRP was associated with reduced pain level (OR: 0.95, 95% CI: 0.91-0.99, for each 1-point increase in pain score), self-reported lack of physical activity (OR: 0.84, 95% CI: 0.72-0.98) and longer sick leave (OR: 1.03, 95% CI: 1.01-1.05, for 30 more days of sick leave). CONCLUSION: In this multicentric observational study, referral to an FRP was linked to pain, self-reported physical activity and sick leave but not medical characteristics assessed. These findings confirm the bio-psycho-social approach of FRPs for cLBP.

8.
Qual Life Res ; 28(11): 3047-3054, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31273625

RESUMO

PURPOSE: To examine the respective and combined impact of "hypothetical" functional impairment (FI) and burden of comorbidities accrual on a 5-year risk of health utility (HU) loss in osteoarthritis (OA). METHODS: Participants of the Knee and Hip Osteoarthritis Long-term Assessment (KHOALA) study with a 5-year follow-up were included. FI, number of comorbidities and HU were measured annually by the WOMAC, Functional Comorbidity Index and Short-Form 6D, respectively. We estimated the population risk of HU loss (PRD: population risk difference, PRR: population risk ratio) under hypothetical FI and comorbidities using the parametric G-formula. Then, mediation analysis investigated the causal mechanism of comorbidities on HU through FI by estimating total, direct and indirect effects. RESULTS: We examined data from 767 patients (68.8% women; 61.6 years). The estimated 5-year risk of HU loss was 47.5% [41.9; 52.2] under natural course and 24.9% [15.5; 34.2] when imposing "Patient acceptable function and No comorbidity" corresponding to a PRD = - 22.6 [- 26.5; - 21.2] and a PRR = 0.5 [0.4; 0.6]. The estimated total risk of HU loss comparing "Two comorbidities" versus "No comorbidity" was significant without mediation effect of FI: Total = 10.1% [6.8; 12.9]; direct = 8.0% [2.7; 13.1]; indirect = 2.1% [- 2.0; 5.2]. CONCLUSIONS: FI and comorbidities are important and independent determinants of HU loss in patient with OA. Half of cases (50%) of HU loss during 5 years could be avoided by preventing comorbidities (30%) and limiting FI under patient acceptable function (20%). Caregivers should additionally pay close attention to the prevention and the treatment of comorbidities in routine management of OA.

11.
J Rheumatol ; 46(9): 1188-1191, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31092709

RESUMO

Flare in knee and hip osteoarthritis (OA) is more than just an exacerbation of pain. Unstructured, semistructured, and focus group interviews followed by Delphi surveys with patients and health professionals (HP) generated candidate domains of an OA flare. Content analysis of interviews with 29 patients and 16 HP extracted 180 statements, which were grouped into 9 clusters. Delphi consensus with 50 patients (Australia, Canada, and France) and 116 HP (17 countries on 4 continents) identified 5 flare domains: pain, swelling, stiffness, psychological aspects, and effect of symptoms. Elements for a preliminary definition of an OA flare are proposed. Registered at clinicaltrials.gov NCT02892058.

12.
Ann Rheum Dis ; 78(7): 890-898, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31040122

RESUMO

OBJECTIVE: To evaluate clinical outcomes in patients who changed treatment from adalimumab to baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, during a phase III programme. METHODS: In phase III RA-BEAM, patients were randomised 3:3:2 to placebo, baricitinib 4 mg once daily, or adalimumab 40 mg biweekly. At week 16 or subsequent visits, non-responders were rescued to open-label baricitinib 4 mg. At week 52, patients could enter a long-term extension (LTE) and continue on baricitinib or switch from adalimumab to baricitinib 4 mg with no adalimumab washout period. Percentage of patients achieving low disease activity and remission were assessed, along with physical function, patient's assessment of pain, and safety. RESULTS: Thirty-five (7%) baricitinib-treated and 40 (12%) adalimumab-treated patients were rescued to baricitinib in RA-BEAM; 78% (381/487) of baricitinib-treated and 72% (238/330) of adalimumab-treated patients who were not rescued in RA-BEAM, entered the LTE and continued/were switched to baricitinib. In both baricitinib-rescued and adalimumab-rescued patients, there were significant improvements in all measures up to 12 weeks after rescue compared with the time of rescue. Patients who switched from adalimumab to baricitinib showed improvements in disease control through 12 weeks in the LTE. Exposure-adjusted incidence rates for treatment-emergent adverse events (TEAEs) and infections, including serious events, were similar for patients who switched from adalimumab to baricitinib and those who continued on baricitinib. CONCLUSIONS: Switching from adalimumab to baricitinib (without adalimumab washout) was associated with improvements in disease control, physical function and pain during the initial 12 weeks postswitch, without an increase in TEAEs, serious adverse events or infections. TRIAL REGISTRATION NUMBERS: NCT01710358, NCT01885078.

14.
Arthritis Res Ther ; 21(1): 63, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30782174

RESUMO

INTRODUCTION: Health-related quality of life (HRQoL) is a priority for patients. The objectives were to describe the changes in HRQoL over 5-8 years in patients with early arthritis (EA) or early inflammatory back pain (IBP) and to explore factors associated to HRQoL. PATIENTS AND METHODS: In 2 prospective observational French cohorts (ESPOIR for EA patients and DESIR for early IBP patients), HRQoL was assessed regularly over 5-8 years, using the SF36 physical and mental composite scores (PCS and MCS, range 0-100). Disease activity was assessed by DAS28-ESR and ASDAS-CRP. Univariate and multivariate linear mixed-effect models and trajectory-based mapping were applied. RESULTS: In all, 1347 patients (701 EA and 646 early IBP) were analysed: mean age 48.4 ± 12.2 and 33.9 ± 8.7 years respectively; mean disease duration 3.4 ± 1.7 and 18.2 ± 10.8 months; and 76.3% and 55.0% females. At baseline, in EA, mean PCS and MCS were respectively 40.2 ± 9.1 and 40.4 ± 11.2 and, in early IBP, were respectively 38.5 ± 8.5 and 39.8 ± 10.9. Over follow-up, HRQoL mean levels improved mostly over the first 6 months (p <  0.001). Two trajectories were evidenced in both diseases. The 'good HRQoL' trajectory groups, i.e. 54-61% of patients, reached levels of HRQoL close to population norms. DAS28-ESR and ASDAS-CRP over time were related to PCS (range of explained variance 9-43%, p <  0.001 in the mixed models) but not to MCS. CONCLUSION: HRQoL was altered similarly for both physical and mental aspects in EA and early IBP. Disease activity only partly explained HRQoL: the drivers of HRQoL should be further explored.

15.
Arthritis Res Ther ; 21(1): 53, 2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755262

RESUMO

OBJECTIVES: Adult-onset Still's disease (AOSD) phenotype appears to be dichotomized in systemic or chronic articular forms. As biologicals and particularly interleukin (IL)-1 and IL-6 blockers play a more and more prominent role in the treatment, their place requires clarification. This study aimed to identify factors predictive of treatment response to anakinra or tocilizumab and investigate whether the choice of biotherapy and delays in the initiation of biotherapy influenced the likelihood of steroid discontinuation. METHODS: A multicenter exploratory retrospective study included all patients diagnosed with AOSD and receiving biological treatments in three regional hospitals until 2018. Clinical and biological characteristics at diagnosis and treatment-related data were collected. The nonparametric Mann-Whitney test was used to perform univariate analysis for quantitative variables, and Fisher's exact test was used for qualitative variables. RESULTS: Twenty-seven patients were included. All but one patient achieved remission with either anakinra or tocilizumab. Treatment responses depended on disease phenotype: the presence of arthritis and a chronic articular phenotype were associated with a substantial response to tocilizumab with p = 0.0009 (OR 36 [2.6-1703]) and p = 0.017 (OR 10 [1.22-92.6]), respectively, whereas the systemic form and the absence of arthritis were associated with a substantial response to anakinra with p = 0.0009 (OR 36 [2.6-1703]) and p = 0.017 (OR 10 [1.22-92.6]), respectively. Tocilizumab increased the likelihood of corticosteroid withdrawal (p = 0.029) regardless of delays in initiation or when it was initiated relative to other treatment in the overall therapeutic strategy. CONCLUSION: This study highlights the therapeutic implications of the phenotypic dichotomy of AOSD and should help us better codify AOSD treatment.

16.
Rheumatology (Oxford) ; 58(6): 1056-1064, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649524

RESUMO

OBJECTIVES: This post hoc analysis of the TOZURA study programme evaluated the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) as monotherapy or with concomitant conventional synthetic DMARDs (csDMARDs) in patients with RA categorized by baseline glucocorticoid (GC) use. METHODS: TOZURA was a multinational, open-label, single-arm, common-framework study programme (11 protocols, 22 countries) in patients with moderate to severe RA in whom csDMARDs or biologic therapies had failed or who were MTX naïve. Patients received once-weekly TCZ-SC 162 mg for ⩾24 weeks as monotherapy or in combination with csDMARDs and/or oral GC use (⩽10 mg/day prednisone or equivalent), which was to be continued unchanged for 24 weeks. Treatment subgroups were defined by baseline GC use and analysed for efficacy and safety. RESULTS: Of 1804 patients who received TCZ-SC, 145 received monotherapy + GC, 208 received monotherapy without GC, 730 received combination therapy + GC and 721 received combination therapy without GC. The median GC dose in both GC subgroups was 5 mg/day. The proportion of patients who achieved clinical remission, defined as DAS in 28 joints using ESR <2.6, increased similarly from baseline to week 24 in all subgroups. Improvements in patient-reported outcomes were similar in all subgroups. Overall adverse event profiles were generally similar between subgroups, with some slight numerical differences between GC and non-GC subgroups. CONCLUSION: The incremental efficacy benefits of TCZ-SC as monotherapy and in combination with csDMARDs were similar between patients with and without previous and continued oral GC treatment, with generally similar safety profiles. TRIAL REGISTRATION: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT01941940, NCT01941095, NCT01951170, NCT01987479, NCT01988012, NCT01995201, NCT02001987, NCT02011334, NCT02031471, NCT02046603, NCT02046616.

17.
Ann Rheum Dis ; 2018 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-30472651

RESUMO

OBJECTIVE: Regulatory T cells (Tregs) prevent autoimmunity and control inflammation. Consequently, any autoimmune or inflammatory disease reveals a Treg insufficiency. As low-dose interleukin-2 (ld-IL2) expands and activates Tregs, it has a broad therapeutic potential. AIM: We aimed to assess this potential and select diseases for further clinical development by cross-investigating the effects of ld-IL2 in a single clinical trial treating patients with 1 of 11 autoimmune diseases. METHODS: We performed a prospective, open-label, phase I-IIa study in 46 patients with a mild to moderate form of either rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Behcet's disease, granulomatosis with polyangiitis, Takayasu's disease, Crohn's disease, ulcerative colitis, autoimmune hepatitis and sclerosing cholangitis. They all received ld-IL2 (1 million IU/day) for 5 days, followed by fortnightly injections for 6 months. Patients were evaluated by deep immunomonitoring and clinical evaluation. RESULTS: ld-IL2 was well tolerated whatever the disease and the concomitant treatments. Thorough supervised and unsupervised immunomonitoring demonstrated specific Treg expansion and activation in all patients, without effector T cell activation. Indication of potential clinical efficacy was observed. CONCLUSION: The dose of IL-2 and treatment scheme used selectively activate and expand Tregs and are safe across different diseases and concomitant treatments. This and preliminary indications of clinical efficacy should licence the launch of phase II efficacy trial of ld-IL2 in various autoimmune and inflammatory diseases. TRIAL REGISTRATION NUMBER: NCT01988506.

18.
Artigo em Inglês | MEDLINE | ID: mdl-30420245

RESUMO

OBJECTIVES: To evaluate the incidence of anti-drug antibody (ADA) occurrences and ADA-related risk factors under adalimumab and infliximab treatment in rheumatoid arthritis (RA) patients. METHODS: The study combined retrospective cohorts from the ABIRISK project totaling 366 RA patients treated with adalimumab (n = 240) or infliximab (n = 126), 92.4% of them anti-TNF naive (n = 328/355) and 96.6% of them co-treated with methotrexate (n = 341/353) with up to 18 months follow-up. ADA positivity was measured by enzyme-linked immunosorbent assay. The cumulative incidence of ADA was estimated, and potential bio-clinical factors were investigated using a Cox regression model on interval-censored data. RESULTS: ADAs were detected within 18 months in 19.2% (n = 46) of the adalimumab-treated patients and 29.4% (n = 37) of the infliximab-treated patients. The cumulative incidence of ADA increased over time. In the adalimumab and infliximab groups, respectively, the incidence was 15.4% (5.2-20.2) and 0% (0-5.9) at 3 months, 17.6% (11.4-26.4) and 0% (0-25.9) at 6 months, 17.7% (12.6-37.5) and 34.1% (11.4-46.3) at 12 months, 50.0% (25.9-87.5) and 37.5% (25.9-77.4) at 15 months and 50.0% (25.9-87.5) and 66.7% (37.7-100) at 18 months. Factors associated with a higher risk of ADA development were: longer disease duration (1-3 vs. < 1 year; adalimumab: HR 3.0, 95% CI 1.0-8.7; infliximab: HR 2.7, 95% CI 1.1-6.8), moderate disease activity (DAS28 3.2-5.1 vs. < 3.2; adalimumab: HR 6.6, 95% CI 1.3-33.7) and lifetime smoking (infliximab: HR 2.7, 95% CI 1.2-6.3). CONCLUSIONS: The current study focusing on patients co-treated with methotrexate for more than 95% of them found a late occurrence of ADAs not previously observed, whereby the risk continued to increase over 18 months. Disease duration, DAS28 and lifetime smoking are clinical predictors of ADA development.

19.
Artigo em Inglês | MEDLINE | ID: mdl-30421978

RESUMO

OBJECTIVES: Osteoporosis is a major risk factor for fracture and treatment is mainly preventive. Patients with severe psychiatric condition and treated with antipsychotics are at risk for vitamin D deficiency and iatrogenic hyperprolactinemia, two serious risk factors of osteoporosis. We aim to determine whether all antipsychotics are similar regarding the risk of osteoporosis in young patients. METHODS: From January 2009 to March 2015, we determined the vitamin D blood level (VDBL) among 484 inpatients and from January 2012 to March 2015, we determined the prolactin blood level (PBL) among 205 inpatients. We systematically recorded well-documented risk factors (e.g., age, gender, ethnic origin, body mass index, or season) and suspected risk factors (e.g., disease type or antipsychotic treatment). RESULTS: Up to 89% of the inpatients had a VDBL under the recommended threshold. Up to 60% of the inpatients had hyperprolactinemia. The multivariate model found a significant effect on VDBL for seasonality (higher VDBL in summer), ethnicity (lower VDBL in Black individuals), and treatment exposure. The multivariate model found a significant effect on PBL for gender and treatment exposure. In both models, aripiprazole had a safer profile compared with other antipsychotics. CONCLUSION: Because adolescence is a period of bone construction and a critical window of opportunity for maximizing bone mass, we recommend vitamin D supplementation in young patients with severe mental condition. It could be interesting to reconsider to regularly monitor PBL among youth patients treated with antipsychotic, with the exception of aripiprazole.

20.
Joint Bone Spine ; 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30315988

RESUMO

The 2014 French Society for Rheumatology (Société Française de Rheumatologie, SFR) recommendations about the management of rheumatoid arthritis (RA) have been updated by a task force composed of 12 expert rheumatologists, 2 patient self-help group representatives, and an occupational therapist. The material used by the task force included recent EULAR recommendations, a systematic literature review, and expert opinion. Four general principles and 15 recommendations were developed. The general principles emphasize the need for shared decision-making between the rheumatologist and the patient and for a global management program including both pharmacological and nonpharmacological treatments. The recommendations deal with the diagnostic strategy for RA, treatment targets, management organization, drug selection based on the treatment line and prognostic factors, management of remissions, and global patient management. Disease-modifying antirheumatic drug (DMARD) therapy should be started as early as possible. Validated composite scores should be determined at regular intervals to assess disease activity -- according to the tight disease control concept -- to achieve the treatment target, i.e., a remission. Methotrexate is the recommended first-line DMARD. The treatment should be optimized when methotrexate is poorly tolerated or inadequately effective. While waiting for conventional synthetic DMARDs to take effect, glucocorticoid therapy can be used, for a brief period to keep the cumulative dose low. When a sustained remission without structural progression is achieved in a patient who is not taking glucocorticoid therapy, targeted therapy de-escalation according to tight disease control principles should be considered. Patients should be periodically screened for comorbidities and their risk factors, which should be evaluated and treated.

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