Carlos Abud-Mendoza

Objective: The purpose of this study was to assess the pharmacokinetics, effectiveness, safety, and immunogenicity of certolizumab pegol (CZP) in polyarticular‐course juvenile idiopathic arthritis (pcJIA). Methods: Pediatric Arthritis Study of Certolizumab Pegol (NCT01550003), a multicenter, open‐label study, enrolled patients aged 2 to 17 years with active pcJIA and inadequate response or intolerance to at least one disease‐modifying antirheumatic drug. Original CZP doses, based on pharmacokinetic model simulations, included loading and then 50, 100, or 200 mg maintenance doses once every two weeks for patients 10 to <20, 20 to 79.0% by Wk12) and associated with lower CZP concentrations, but it maintained response to CZP. Conclusion: Open‐label CZP treatment demonstrated rapid, long‐term clinical improvements, an acceptable safety profile, and tolerability in patients with pcJIA. No new safety signals were identified.

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: We evaluate tofacitinib efficacy and safety in patients with juvenile idiopathic arthritis (JIA) stratified by concomitant methotrexate and prior biologic disease‐modifying antirheumatic drug (bDMARD) treatment. Methods: In this two part, double‐blind, randomized withdrawal Phase 3 trial (NCT02592434), patients (2–<18 years) with JIA received open‐label tofacitinib (5 mg twice daily/weight‐based equivalent) in Part 1 (Day 1–Week 18). Those eligible were randomized to continue tofacitinib or switch to placebo in Part 2 (Weeks 18–44). In this post hoc analysis, patients were stratified by concomitant methotrexate (MTX+/−) and prior bDMARD treatment (bDMARD+/−). Efficacy outcomes included JIA disease flare, JIA/American College of Rheumatology (ACR) 50/70 response rates, and JIA/ACR clinical inactive disease (CID). Safety was assessed throughout the trial. Results: Of 225 patients in Part 1, 147 (65.3%) were MTX+; 85 (37.8%) were bDMARD+. Across subgroups, JIA flare rate at Week 44 was lower with tofacitinib than placebo: patients who were MTX+ (29.8% vs 47.5%), patients who were MTX− (32.3% vs 73.1%), patients who were bDMARD+ (29.0% vs 70.4%), patients who were bDMARD− (31.6% vs 48.3%). Greater JIA/ACR50/70 and JIA/ACR‐CID responses with tofacitinib than with placebo were observed across subgroups. In tofacitinib‐treated patients, adverse events (AEs) were more common in the subgroups of patients who were MTX− (85.9%) and patients who were bDMARD+ (81.2%) than the subgroups of patients who were MTX+ (74.1%) and patients who were bDMARD− (76.4%). Similar findings were observed with serious AEs/discontinuations due to AEs. Conclusion: Tofacitinib was efficacious for patients regardless of baseline concomitant MTX treatment or prior bDMARD exposure; MTX may have a protective effect for flare upon tofacitinib withdrawal. Safety was consistent with the known tofacitinib profile, and no new risks were identified in these subgroups.

Objective: To evaluate rates of clinically inactive disease (CID) and remission in patients with juvenile idiopathic arthritis (JIA) receiving tofacitinib using the 2021 Juvenile Arthritis Disease Activity Score (JADAS) thresholds and American College of Rheumatology (ACR) criteria. Methods: This post hoc analysis included patients with active JIA (polyarticular-course JIA, psoriatic arthritis, or enthesitis-related arthritis) enrolled in a phase III randomized withdrawal study of tofacitinib. In part 1 (weeks 0-18), patients received open-label tofacitinib. In part 2 (weeks 18-44), patients who achieved ACR improvement ≥ 30% were randomized to tofacitinib or placebo for 26 weeks or until JIA flare. Disease activity was assessed using the JADAS in 10 joints (JADAS10) based on C-reactive protein, with interpretation according to 2021 polyarthritis thresholds. JADAS10 remission was defined as ≥ 24 continuous weeks of JADAS10 CID (JADAS10-CID). ACR CID (ACR-CID) and ACR clinical remission were also assessed. Results: Of 225 patients with JIA in part 1, 173 (76.9%) were randomized in part 2 to continue tofacitinib or switch to placebo. Rates of JADAS10-CID and ACR-CID increased throughout part 1 to 30.5% and 15.8% (week 18), respectively. In part 2, these were sustained with tofacitinib (week 44: 35.2% [JADAS10-CID], 25% [ACR-CID]) and decreased when patients switched to placebo (week 44: 25.9% [JADAS10-CID], 15.3% [ACR-CID]). A small proportion of patients achieved JADAS10 remission at week 44 (tofacitinib: 14.8%; placebo: 7.1%). Conclusion: In patients with JIA receiving tofacitinib, JADAS10-CID and ACR-CID rates improved rapidly and were sustained over time, and a small proportion of patients achieved JADAS10 remission. Inactive disease is a feasible treatment target in patients receiving tofacitinib. (ClinicalTrials.gov: NCT02592434)

Herpes zoster (HZ) is a common disease in older adults and immunocompromised patients, and is frequently associated with long-term complications that impact quality of life. Fortunately, more than one vaccine against HZ is now available in Mexico. Two expert consensus groups discussed adult vaccination strategies in Mexico, focusing on HZ in older adults and immunocompromised individuals; their insights are reported here. HZ is usually treated inappropriately in Mexico. Late diagnosis and suboptimal management are common, as is a lack of treatment options, particularly for pain, which is often unresponsive to standard painkillers. Improving vaccination rates against HZ in Mexico is therefore important, but several barriers to HZ vaccination exist. It is not included in the national vaccination schedule, where included vaccines usually have higher coverage. Actions to overcome barriers include improving awareness of HZ and vaccine availability, developing and promoting guidelines and recommendations for vaccination, and expanding access and infrastructure for vaccination.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease that often requires hospitalization. Most hospitalizations are due to infections and/or disease activity, for which several risk factors have been described in non-Mestizo patients. Objective: To identify risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). Methods: This was an observational case-control study of patients with SLE in San Luis Potosí, Mexico, evaluated from January 2019 to October 2020. We compared hospitalized lupus patients with non-hospitalized lupus patients. We used descriptive statistics and logistic regression to describe potential risk factors. Results: Of a total of 202 patients, 89 (45.1%) were hospitalized; these patients were younger, had shorter disease duration, higher disease activity scores (systemic lupus erythematosus disease activity index-SLEDAI), and more accumulated damage than non-hospitalized patients. The primary reasons for hospitalization were disease activity (60.7%), kidney disease, infection, and drug toxicity (5.6%). Multivariate analysis revealed several risk factors associated with hospitalization, including elevated creatinine, C-reactive protein, neutrophil levels, and constitutional symptoms, while prolonged international normalized ratio (INR), longer stay in the intensive care unit (ICU), and vasopressor use were associated with mortality. The use of antimalarials was a protective factor against hospitalization. Survival analysis revealed that patients with hospital-acquired infections had a lower probability of survival. Conclusions: Disease activity was the most common reason for hospitalization; kidney, constitutional, and hematological factors were associated with hospitalization; and the use of antimalarial was a protective factor for hospitalization.