Predictive factors of flares in systemic lupus erythematosus patients: data from a multiethnic Latin American cohort.

Purpose The purpose of this paper is to determine the factors predictive of flares in systemic lupus erythematosus (SLE) patients. Methods A case-control study nested within the Grupo Latino Americano De Estudio de Lupus (GLADEL) cohort was conducted. Flare was defined as an increase ≥4 points in the SLEDAI. Cases were defined as patients with at least one flare. Controls were selected by matching cases by length of follow-up. Demographic and clinical manifestations were systematically recorded by a common protocol. Glucocorticoid use was recorded as average daily dose of prednisone and antimalarial use as percentage of time on antimalarial and categorized as never (0%), rarely (>0-25%), occasionally (>25%-50%), commonly (˃50%-75%) and frequently (˃75%). Immunosuppressive drugs were recorded as used or not used. The association between demographic, clinical manifestations, therapy and flares was examined using univariable and multivariable conditional logistic regression models. Results A total of 465 cases and controls were included. Mean age at diagnosis among cases and controls was 27.5 vs 29.9 years, p = 0.003; gender and ethnic distributions were comparable among both groups and so was the baseline SLEDAI. Independent factors protective of flares identified by multivariable analysis were older age at diagnosis (OR = 0.929 per every five years, 95% CI 0.869-0.975; p = 0.004) and antimalarial use (frequently vs never, OR = 0.722, 95% CI 0.522-0.998; p = 0.049) whereas azathioprine use (OR = 1.820, 95% CI 1.309-2.531; p < 0.001) and SLEDAI post-baseline were predictive of them (OR = 1.034, 95% CI 1.005-1.064; p = 0.022). Conclusions In this large, longitudinal Latin American cohort, older age at diagnosis and more frequent antimalarial use were protective whereas azathioprine use and higher disease activity were predictive of flares.

Early referral and control of disease's flares prevent Orthopedic and Hand Surgery Indication (OHSI) in a dynamic cohort of Hispanic early rheumatoid arthritis patients.

BACKGROUND: Reconstructive joint surgery is an indicator of poor prognosis in rheumatoid arthritis (RA). Objectives of this study were to describe the incidence rate of orthopedic and hand surgery indication (OHSI) in an ongoing cohort of Hispanic early RA patients treated according to a T2T strategy and to investigate predictors. METHODS: Through February 2018, the cohort comprised 185 patients recruited from 2004 onwards, with variable follow-up, and rheumatic assessments at fixed intervals that included prospective determination of OHSI. Charts were reviewed by a single data abstractor. OHSI incidence rate was calculated. A case-control study nested within a cohort investigated the predictors; cases (OHSI patients) were paired with controls (1:4) according to age, sex and autoantibodies. A logistic regression model included baseline and cumulative (up to OHSI or equivalent) variables related to disease activity, treatment and to persistence with therapy. The IRB approved the study. RESULTS: Patients from the cohort were predominantly middle-aged (mean ± SD age: 38.5 ± 12.9 years) females (87.6%) with 5.4 ± 2.6 months of disease duration. The cohort contributed to 1538 patient-years of follow-up. Twelve patients received incidental OHSI at a follow-up of 85 ± 44.5 months. The OHSI incident global rate was 8/1000 patient-years. Longer symptom duration at cohort referral (OR: 1.313, 95%CI: 1.02-1.68, p = 0.032) and a higher number of flares/patient (OR: 1.608, 95%CI: 1.05-1.61, p = 0.015) predicted OHSI. OHSI patients had more severe flares than their counterparts, and the opposite figure was true for mild flares. CONCLUSION: Early referral for appropriate management and flare control may prevent OHSI in Hispanic recent-onset RA patients.

The added value of musculoskeletal ultrasound to clinical evaluation in the treatment decision of rheumatoid arthritis outpatients: physician experience matters.

BACKGROUND: Musculoskeletal ultrasound improves the accuracy of detecting the level of disease activity (DA) in RA patients, although its impact on the final treatment decision in a real clinical setting is uncertain. The objectives were to define the percentage of clinical scenarios from an ongoing cohort of RA outpatients in which the German Ultrasound Score on 7 joints (GUS-7) impacted the treatment and to explore if the impact differed between a senior rheumatologist (SR) vs. a trainee (TR). METHODS: Eighty-five consecutive and randomly selected RA outpatients underwent 170 assessments, 85 each by the SR and the TR. Initially, both physicians (blinded to each other) performed a rheumatic assessment and recommended a preliminary treatment. Then, the patients underwent the GUS-7 evaluation by an experienced rheumatologist blinded to clinical evaluations; selected joints of the clinically dominant hand were assessed by gray-scale and power Doppler (PD). In the final step, the TR and the SR integrated the GUS-7 findings with their previous evaluation and reviewed their recommendations. The patients received the final recommendation from the SR to avoid patient confusion. The study was approved by the Internal Review Board and all the patients signed informed consent. GUS-7 usefulness was separately evaluated by the SR and the TR according to a visual analogue scale (0 = not useful at all, 10 = very useful). Descriptive statistics were used. RESULTS: The patients were primarily middle-aged females (91.4%) with (mean ± SD) disease duration of 7.5 ± 3.9 years. The majority of them (69.2% according to TR and 71.8% to SR) were in DAS28-ESR-remission. In 34 of 170 clinical scenarios (20%), the GUS-7 findings modified the final treatment proposal; 24 of these scenarios were determined by the TR vs. 10 by the SR: 70.5% vs. 29.5%, p = 0.01. Treatment changes (increase, decrease and joint injection) were similar between both specialists. As expected, the TR rated the GUS-7 usefulness higher than the SR, particularly in the clinical scenarios where the GUS-7 findings impacted treatment. CONCLUSIONS: Musculoskeletal ultrasound added to standard rheumatic assessments impacted the treatment proposal in a limited number of patients; the impact was greater in the TR.

Late-onset systemic lupus erythematosus in Latin Americans: a distinct subgroup?

OBJECTIVE: To examine the characteristics of patients who developed late onset systemic lupus erythematosus (SLE) in the GLADEL (Grupo Latino Americano de Estudio del Lupus) cohort of patients with SLE. METHODS: Patients with SLE of less than two years of disease duration, seen at 34 centers of nine Latin American countries, were included. Late-onset was defined as >50 years of age at time of first SLE-related symptom. Clinical and laboratory manifestations, activity index (SLEDAI), and damage index (SLICC/ACR- DI) were ascertained at time of entry and during the course (cumulative incidence). Features were compared between the two patient groups (<50 and ≥50) using descriptive statistics and hypothesis tests. Logistic regression was performed to examine the association of late-onset lupus, adjusting for other variables. RESULTS: Of the 1480 patients included, 102 patients (6.9 %) had late-onset SLE, 87% of which were female. Patients with late-onset SLE had a shorter follow-up (3.6 vs. 4.4 years, p < 0.002) and a longer time to diagnosis (10.1 vs. 5.8 months, p < 0.001) compared to the younger onset group. Malar rash, photosensitivity, and renal involvement were less prevalent while interstitial lung disease, pleural effusions, and sicca symptoms were more frequent in the older age group (p > 0.05). In multivariable analysis, late onset was independently associated with higher odds of ocular (OR = 3.66, 95% CI = 2.15-6.23), pulmonary (OR = 2.04, 95% CI = 1.01-4.11), and cardiovascular (OR = 1.76, 95% CI = 1.04-2.98) involvement and lower odds of cutaneous involvement (OR = 0.41, 95% CI = 0.21-0.80), number of cumulative SLE criteria (OR = 0.79, 95% CI = 0.64-0.97), use of cyclophosphamide (OR = 0.47, 95% CI = 0.24-0.95), and anti-RNP antibodies (OR = 0.43, 95% CI = 0.20-0.91). A Cox regression model revealed a higher risk of dying in older onset than the younger-onset SLE (OR = 2.61, 95% CI = 1.2-5.6). CONCLUSION: Late-onset SLE in Latin Americans had a distinct disease expression compared to the younger-onset group. The disease seems to be mild with lower cumulative SLE criteria, reduced renal/mucocutaneous involvements, and less use of cyclophosphamide. Nevertheless, these patients have a higher risk of death and of ocular, pulmonary, and cardiovascular involvements.

Early disease activity suppression and younger age predict excellent outcome of recent-onset rheumatoid arthritis patients treated with conventional disease modifying anti-rheumatic drugs.

OBJECTIVES: Sustained remission (SR) is the target of treatment offered to patients with rheumatoid arthritis (RA). The objective of the present paper is to describe predictors of favourable outcomes in a cohort of early RA patients. METHODS: Data from 89 patients with 3 years of consecutive assessments and traditional treatment were analysed. SR was defined as ≥ 6 consecutive months with 2011 ACR/EULAR remission criteria. Excellent outcome (EO) was defined according to patient's perception. Descriptive statistics, logistic regression models and Cox regression were used. RESULTS: At baseline, patients were predominantly females (n=78), had rheumatoid factor (n=70) and (mean ± SD) age of 38.8 ± 13.6 years. After (mean ± SD) 37.1 ± 2.5 months, 75 patients achieved ≥ 1 SR state and 35 an EO. The former had lower disease activity, disability and comorbidity and better functional status at baseline than their counterparts (p ≤ 0.05); they also accumulated lesser disability (p ≤ 0.03). Lower C-reactive protein and disease activity and lesser comorbidity predict SR (p ≤ 0.04). Patients with EO were younger, better educated, had lower disease activity, better functional status and lesser comorbidity at baseline than their counterparts (p ≤ 0.05). They achieved a first sustained remission state (p ≤ 0.001) sooner and accumulated lesser disability and incident erosive disease (p ≤ 0.002). Younger age and lower disease activity were prognosticators of EO (p ≤ 0.02). When age, baseline disease activity and time to first SR were investigated as predictors of EO, younger age (HR:0.95, 95% CI: 0.91-0.98, p=0.003) and earlier SR (HR:0.49, 95% CI: 0.39-0.61, p ≤ 0.001) were relevant. CONCLUSIONS: Younger patients with lower disease activity achieved earlier SR which, in addition to age, was predictor of EO.

Persistence on therapy is a major determinant of patient-, physician- and laboratory- reported outcomes in recent-onset rheumatoid arthritis patients.

OBJECTIVES: To evaluate impact of persistence on therapy on sustained major patient-, physician- and laboratory-reported outcomes (PROs, PHYROs and LAROs, respectively) in 112 recent-onset rheumatoid arthritis (RA) patients. METHODS: At each visit a rheumatologist interviewed patients regarding therapy, morning stiffness and fatigue, scored the 28-joint disease activity score and a visual analogue scale (VAS) and determined acute-phase-reactants. The patients completed the Hispanic version of the Rheumatoid Arthritis Disease Activity Index, the Medical Outcome Short Form 36 (SF-36), the Health Assessment Questionnaire (HAQ), a pain-VAS and an overall-disease activity-VAS. Persistence was defined by self-report through directed interview. Sustained major PROs, PHYROs and LAROs were defined according to cut-offs, when maintained for ≥6 months and until last follow-up. Descriptive statistics, Kaplan-Meier curves and Cox models were used. RESULTS: Total person-time of receiving therapy was of 375.5 patient-years. From February 2004 to June 2009, 36 (32.1%) patients were persistent. Baseline PROs/PHYROs/LAROs showed active disease and poor health status in both groups, but persistent patients (PP) had significantly lower HAQ (p=0.03) and overall-disease activity-VAS (p=0.01). More PP reached a sustained major SF-36-physical function-score (p=0.02). Persistence was the greatest independent risk factor for sustained major PROs (but absence of fatigue) and PHYROs, (p≤0.04). Time from baseline to major and sustained PROs (excluded absence of fatigue), PHYROs and C-reactive protein were shorter in PP (p≤0.04). CONCLUSIONS: Persistence was a strong predictor for major and sustained outcomes in early RA. Favourable outcomes appear earlier in persistent than in non-persistent patients.

Purified protein derivative reaction in systemic lupus erythematosus patients. Indirect study of cellular immunity.

Cutaneous anergy in SLE patients results from disease activity and/or immunosuppressive treatment (IT). The aim of this study was to evaluate purified protein derivative (PPD) reaction in SLE patients. A total of 145 patients and 20 controls were studied. Five units of PPD were applied on day 0, and skin reaction was measured after 3 (PPD1) and 6 (PPD2) days. A booster was applied (day 14), and the reaction was measured after 3 (PPD3) and 6 (PPD4) days. Non-parametric ANOVA test and unpaired Student's t-test were performed. Forty patients (group I) were inactive (MexSLEDAI < 3), receiving no IT (at least 3 months previous to the PPD test); 39 (group II) were inactive receiving IT; 24 (group III) were active without IT, and 42 (group IV) were active with IT. Active patients had lower PPD1 (group III, 1.4 +/- 0.9; group IV, 0.6 +/- 0.5) than inactive patients (group I, 8.4 +/- 2.3; group II, 5.1 +/- 1.9) and than controls (9.4 +/- 3; P < or = 0.001). Group IV had lower delayed response (PPD2 = 0.3 +/- 0.3) than inactive groups (group I, 2.6 +/- 0.9; group II, 3.1 +/- 0.8) and than controls (7.9 +/- 2.5; P < or = 0.001). Group III had lower delayed reaction (PPD2 = 1.2 +/- 0.8) than controls (P < or = 0.001). Active SLE patients, receiving or not receiving IT, had lower skin response to PPD than inactive patients and controls.