Graciela S. Alarcon

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which accurate assessment of disease activity is essential for optimizing treatment strategies. Hematological indices derived from routine blood tests, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), have been proposed as accessible markers of systemic inflammation. Objectives: To investigate the association between NLR, PLR, and SII and disease activity in patients with RA. Methods: A total of 188 patients with RA from a tertiary referral center in Peru were included. Disease activity was assessed using the Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP) and serum C-reactive protein (CRP). The Spearman correlation analyses were performed to examine associations between hematological indices and disease activity measures. Multivariable generalized linear models were used to determine independent associations after adjusting for potential confounders, including age, sex, disease duration, corticosteroid dose, and disease-modifying antirheumatic drug (DMARD) therapy. Results: Neutrophil-to-lymphocyte ratio, PLR, and SII showed significant positive correlations with DAS28-CRP ( r = 0.66, r = 0.47, and r = 0.57, respectively) and CRP levels ( r = 0.69, r = 0.43, and r = 0.62, respectively) (all P < .001). In multivariable analyses, all 3 indices remained independently associated with both DAS28-CRP and CRP after adjustment for confounding variables (all P < .001). Conclusion: Hematological indices such as NLR, PLR, and SII are significantly associated with disease activity in RA and may represent simple and cost-effective complementary biomarkers for disease monitoring, particularly in resource-limited settings like in Latin America. Design: Retrospective cross-sectional study.

Aim: To evaluate the factors associated with changes in self-efficacy in systemic lupus erythematosus (SLE) patients from a prevalent cohort. Methods: Members of the Almenara Lupus Cohort who had entered it between 2018 and 2024 were included. Sociodemographic variables were collected. Self-efficacy was examined with the five domains of the PROMIS self-efficacy for the management of chronic conditions’ instrument and general self-efficacy. The Short Form (SF)-36 health questionnaire’ [physical and mental component summary measures (PCS and MCS)] was obtained. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and damage with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Therapeutic variables included the use of antimalarials and of immunosuppressants as well as the daily prednisone dose. Generalized estimating equations were performed using general self-efficacy and the five domains for chronic disease management as outcomes. Results: 331 patients were included; their mean age at diagnosis was 35.1 (SD = 13.7) years and 91.5% their disease duration at baseline was 10.3 (SD = 7.49) years; ( n = 303) were women; 97.9% were Mestizo. Factors associated with a better general self-efficacy were White ethnicity (β = 7.09, SE = 1.14, p < 0.001), being currently employed (β = 1.09, SE = 0.53, p = 0.038), PCS (β = 0.08, SE = 0.02, p < 0.001), and previous general self-efficacy (β = 0.39, SE = 0.05, p < 0.001). In contrast, Black ethnicity (β = −2.06, SE = 0.56, p < 0.001 and daily prednisone dose (β = −0.13, SE = 0.02, p < 0.001) were negatively associated with general self-efficacy. Conclusions: Factors associated with general self-efficacy improvement were higher previous self-efficacy, White ethnicity, being currently employed and having a better HRQoL In contrast, Black ethnicity and higher daily prednisone dose predisposed to general self-efficacy worsening.

Objectives: To compare the treatments used for the first episode of lupus nephritis (LN) in two Latin American cohorts (historical and contemporary) over a 25-year period, and their associations with clinical outcomes. Methods: Patients with biopsy-confirmed first LN episode were classified as non-proliferative (class V) or proliferative (classes III/IV). Sociodemographic, clinical, and treatment variables were described. Propensity score matching was used to examine the associations with four outcomes: mortality, damage accrual (SDI), hospitalization, and end-stage renal disease (ESRD). Results: A total of 532 SLE patients were included: 362 from GLADEL 1.0 (historical cohort) and 170 from GLADEL 2.0. (contemporary). Compared to GLADEL 1.0, patients in GLADEL 2.0 received lower doses of oral glucocorticoids (GC), more frequently GC pulses and antimalarials but less frequently cyclophosphamide. An increase in the use of mycophenolate mofetil and other immunosuppressants was also observed. In the logistic regression models, SDI was associated with baseline SDI and GC pulses, whereas belonging to the GLADEL 2.0 was a protective factor. Mortality was associated with Mestizo ethnicity and partial health coverage; antimalarial was identified as a protective factor. Hospitalizations were associated with baseline SLEDAI and SDI, follow-up time, and lower educational level. Belonging to the GLADEL 2.0 cohort was protective against the occurrence of ESRD. Conclusions: Patients in the contemporary cohort benefited from advances in treatment strategies, with less cumulative damage and progression to ESRD, although mortality remained unchanged. These improvements likely reflect the increased use of newer therapies, more targeted approaches, in line with current treatment guidelines, and better access to specialized care.

Objective: To assess the effect of antimalarials (AMs) on overall damage and on its most frequently affected domains, as measured by the Systemic Lupus International Collaborating Clinics Damage Index (SDI) in patients from the GLADEL cohort. Methods: New damage was defined as a ≥1 point increase in SDI since cohort entry. AMs users were those who received AMs for at least 6 months after entering the cohort. AMs users and non-users were matched for age, sex, ethnicity, and baseline SDI using stratified random sampling. Two comparisons were carried out: patients with and without new damage, and AM users versus non-users. Propensity score matching was used to determine the effect of AM use on the most frequently affected damage domains. Results: A total of 850 patients were included; 419 (49.3%) were AM users and 431 (50.7%) non-users. During a median follow-up of 48.5 (IQR 19.3, 69.0) months, 472 (55.5%) developed damage. The most affected domains were skin (18.4%), renal (14.6%), neuropsychiatric (10.8%), musculoskeletal (6.9%), and cardiovascular (4.5%). AMs use was associated with a lower proportion of patients accruing damage at follow-up (170 [40.6%] vs 208 [48.3%]; p = .028). AMs were protective against overall damage (HR 0.7, 95% CI [0.5–0.9]; p = .002), renal (HR 0.4, 95% CI [0.3–0.6]; p < .001), and neuropsychiatric damage (HR 0.5, 95% CI [0.3–0.9]; p = .022). Conclusion: AM use is independently associated with a lower probability of overall, renal, and neuropsychiatric damage accrual. These findings support early and sustained AM treatment in lupus patients, unless contraindicated.

Objective: Using a hydroxychloroquine (HCQ) dose of 5 mg/kg/day in systemic lupus erythematosus (SLE) is associated with a higher risk of flares; HCQ blood level monitoring could be a better way to adjust the HCQ dose. We studied the upper threshold for a reference range of HCQ levels to inform routine monitoring. Methods: This observational study included patients (N = 2,010) across the Systemic Lupus International Collaborating Clinics, Wisconsin, international, and French studies who underwent HCQ blood level measurements. Using adjusted spline and logistic regression analyses on the cross‐sectional data, we first identified an HCQ blood level associated with higher HCQ toxicity. Next, we tested if this upper threshold level was supratherapeutic (no further risk reduction for the Systemic Lupus Erythematosus Disease Activity Index 2000 [score ≥6]). Finally, we examined associations between chronic kidney disease (CKD) stage and supratherapeutic (toxic) HCQ blood levels. Results: Among 1,842 patients (excluding 168 patients with very low HCQ blood levels), 4.9% had HCQ‐related toxicity. Odds of toxicity were 2.1‐fold higher with blood levels ≥1,150 ng/mL and 1.7‐fold higher with the cumulative HCQ dose per 1,000‐g increase. Blood levels ≥1,150 ng/mL were associated with a saturation in therapeutic effect, indicating supratherapeutic levels. Patients with CKD stage ≥3 had 2.3‐fold higher odds of having supratherapeutic levels (≥1,150 ng/mL). Conclusion: The therapeutic reference range for HCQ blood level monitoring is 750 to <1,150 ng/mL. HCQ level monitoring could optimize HCQ use, particularly in patients with CKD stage ≥3. Future longitudinal studies are needed to validate the use of HCQ blood level monitoring in optimizing dosing. image

Objective: To evaluate the association between the daily glucocorticoid (GC) dose and various patient-reported outcomes (PROs) in patients with systemic lupus erythematosus (SLE) who have achieved Lupus Low Disease Activity State (LLDAS). Methods: Patients from a single-center cohort were included. PROs included the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), Lupus Quality of Life (LupusQoL), physical and mental component summary scores of the 36-Item Short Form Health Survey (SF-36), and the Lupus Foundation of America Rapid Evaluation of Activity in Lupus (LFA-REAL) PRO. Univariable and multivariable generalized estimating equations (GEEs) were performed; the multivariable models were adjusted for possible confounders: age at diagnosis, sex, socioeconomic status, educational level, ethnicity, disease duration, disease activity and damage, and antimalarial and immunosuppressant use. In an alternative analysis, GEE was also performed with patients categorized on the basis of 4 prednisone dose categories: 0, > 0 and ≤ 2.5, > 2.5 and ≤ 5 mg, and > 5 and ≤ 7.5 mg. Results: Three hundred twenty-four patients and 1338 LLDAS visits were included. In the adjusted analysis, the daily GC dose was associated with worse scores in FACIT-F, LFA-REAL PRO, and 4 out of the 8 domains of the LupusQoL. In the alternative analysis, after adjustment, the patients in the high GC dose category had a trend of worse PRO scores in the adjusted analysis, whereas those in the lower GC dose category showed a trend of better PRO scores. Conclusion: The daily GC dose is associated with worse PROs in patients with SLE in LLDAS, even after adjusting for possible confounders.

Objective: To estimate the prevalence of Systemic Lupus Erythematosus (SLE) in Peru in 2017 and its association with altitude, environmental temperature, and physician density. Methods: This ecological study was performed using population data from the 2017 Peruvian census. The number of SLE cases for each department was obtained from the National Health Registries using the ICD-10 code M32. Altitude, environmental temperature and physician density were obtained for each department from the National Institute of Statistics and Informatic ( Instituto Nacional de Estadística e Informática) registries. The prevalence for each department was calculated adjusting for age and sex. Then a negative binomial regression was performed to estimate the prevalence ratio (PR) and evaluate factors associated with the prevalence of SLE. Results: The national prevalence of SLE was 40.2 per 100,000 people. Two age groups had the highest prevalence: 12–17 years and 30–59 years. Females exhibited a higher prevalence than males, particularly in the 30–59 age group (113.9 vs 16.1 per 100,000, respectively). An inverse relationship was observed between the age- and sex-adjusted prevalence in each department and altitude (PR 0.97; 95% CI: 0.94–0.99). On the other hand, there was a direct relationship with physician density (PR: 1.04; 95% CI: 1.01–1.07). No association was found between the adjusted prevalence and environmental temperature or latitude. Conclusion: The prevalence of SLE in Peru aligns with global estimates. The inverse relationship with altitude and the direct association with physician density suggest that environmental and healthcare access factors may influence disease distribution. Further research is needed to explore the underlying mechanisms driving these associations.

Objective: The Systemic Lupus International Collaborating Clinics Frailty Index (SLICC‐FI) as a predictor of quality of life (QoL) in patients with systemic lupus erythematosus (SLE) has not been evaluated longitudinally. We estimated the association of SLICC‐FI scores with future QoL in our prevalent Latin American Mestizo cohort.Methods: Patients from a single‐center SLE cohort were included. Health‐related QoL was ascertained with the LupusQoL tool, and frailty was ascertained with the SLICC‐FI. Generalized estimating equations were performed, using each domain of the LupusQoL as an outcome in the subsequent visit, and the SLICC‐FI (as a continuous variable) in the previous visit. Alternative analyses were also conducted including the SLICC‐FI as a categorical variable. In both approaches, the multivariable models were adjusted for possible confounders (age at diagnosis, sex, socioeconomic status, ethnicity, Systemic Lupus Erythematosus Disease Activity Index 2000, SLICC/American College of Rheumatology damage index [SDI], disease duration at baseline, prednisone daily dose, antimalarial and immunosuppressive drug treatment, and the same domain of the LupusQoL in the previous visit).Results: A total of 428 patients and 2,645 visits were included in this study, and they were observed for 4.71 ± 3.52 years. At baseline, the mean ± SD of disease duration, SDI scores, and SLICC‐FI scores were 7.2 ± 6.6 years, 1.0 ± 1.3, and 0.17 ± 0.05, respectively.In the main analysis, after adjusting for possible confounders, higher SLICC‐FI scores predicted a higher LupusQoL score in the domains of pain, planning, emotional health, and fatigue. In the alternative analyses, after adjustment, the frail and least fit categories were predictive of higher LupusQoL scores in the domain of fatigue, and frailty (SLICC‐FI score of >0.21) predicted worse body image compared with least fit (SLICC‐FI score 0.03–0.10).Conclusion: Higher SLICC‐FI scores predicted worse health‐related QoL as measured by higher LupusQoL scores from patients from the Almenara lupus cohort. Our findings reinforce the prognostic value of this tool in patients with SLE. image

Objectives: To determine the possible predictive value of self-efficacy on fatigue in SLE patients. Methods: SLE patients from a single-center prevalent cohort were included. Self-efficacy was ascertained with the five instruments of the Patient-Reported Outcomes Measurement Information System® (PROMIS®) Self-efficacy for Managing Chronic Conditions plus the PROMIS general self-efficacy. For PROMIS instruments, a score of 50 is the average for a clinical population (people with a chronic condition), the higher score, the greater self-efficacy. Fatigue was ascertained with the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F), the higher score, the lower fatigue. Generalized estimating equations were performed, using as outcome the FACIT-F in the subsequent visit, and the self-efficacy instrument in the previous visit; multivariable models were adjusted for possible confounders. All the confounders were measured in the same visit than the self-efficacy instrument. Results: A total of 209 patients and 563 visits were included. At baseline, FACIT-F was 33.0 (10.2), mean general self-efficacy was 47.2 (10.4), self-efficacy for managing emotions was 44.6 (8.0), for managing symptoms was 47.7 (8.2), for managing daily activities was 45.5 (7.5) for managing social interactions was 42.9 (7.9) and for managing medications and treatment was 43.9 (7.0). In the multivariable models a lower fatigue was predicted by self-efficacy for managing symptoms and managing activities. Conclusion: A better self-efficacy is predictive of a subsequent lower fatigue, even after adjustment for possible confounders. Strategies to improve self-efficacy in SLE patients should be encouraged.