OBJECTIVE: Poor adherence to oral chemotherapy adversely impacts clinical outcomes and escalates overall healthcare costs. Despite barriers to medication adherence, a significant gap remains in assessing adherence to oral chemotherapy among multiple myeloma (MM) patients with lower socioeconomic status. Hence, our study aims to evaluate immunomodulator adherence in MM patients at a county hospital, primarily serving underrepresented and indigent individuals with low socioeconomic status across the greater Houston area.
METHODS: Inclusion criteria composed of patients diagnosed with MM, aged at least 18 years, and treated with lenalidomide or pomalidomide-two widely used immunomodulators-for a minimum of 2 months or having two or more records of dispensation between May 2019 and May 2021. Adherence was gauged using an adjusted version of the medication possession ratio (MPR).
RESULTS: Sixty-two patients were enrolled, yielding a mean MPR value of 88% (SD, ± 18.9). Of these, 43 patients (69.3%) demonstrated adherence with an MPR of ≥ 0.90. A significant difference was found in treatment duration between the adherent (mean 8.8 months; SD, ± 7.2) and non-adherent (mean 13.4 months; SD, ± 7.9) groups (p = 0.027). Notably, race/ethnicity demonstrated a significant difference (p = 0.048), driven by disparities in African American and Hispanic representation across adherence levels.
CONCLUSIONS: In summary, our findings highlight race and treatment duration to be predictors of immunomodulator adherence among MM patients with lower socioeconomic status. Further research is imperative to devise and test innovative interventions aimed at enhancing medication adherence, thereby contributing to improved survival and healthcare quality in this population.

BACKGROUND: Pediatric pemphigus is a rare bullous disease that represents a diagnostic and therapeutic challenge;  evidence on patients\' response to various treatments and long-term surveillance data are lacking. We aimed to investigate pediatric pemphigus patients\' characteristics, diagnosis, therapeutics, response, and long-term follow-up.
METHODS: This is a retrospective study of all pemphigus patients aged <18 years, diagnosed between 2000 and 2023, from three tertiary medical centers in Israel. The diagnosis was confirmed by positive immunofluorescence.
RESULTS: Twelve pediatric pemphigus patients were included (mean age 10.7 ± 4.3 years, male:female ratio 1:1). Mean diagnostic delay was 11.1 ± 12.6 months (range 1.8-36 months). Most patients had pemphigus vulgaris with mucosal involvement (58.3%). First-line treatment for all patients included systemic corticosteroids (sCS), with a treatment duration (including tapering down) of 28 ± 18.4 months. Hospitalization did not yield better outcomes. Only three patients achieved sustained complete response with sCS treatment (25.0%), and the rest required additional therapeutics, most commonly rituximab. Rituximab showed a good safety profile and therapeutic response. Follow-up was recorded up to 18.1 years after diagnosis (mean: 5.6 years). Three of five patients with information available more than 5 years after the pemphigus diagnosis still exhibited disease symptoms.
CONCLUSIONS: Pediatric pemphigus is associated with a significant diagnostic delay. While sCS can induce remission in most patients as a first-line treatment, long-term disease control requires additional immunomodulators. Long-term follow-up reveals a chronic yet mostly benign disease course in this population and advocates for the use of rituximab in pediatric pemphigus patients.

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Background Immunomodulatory therapy for chronic rheumatic disease carries a risk for infectious complications. In Bangladesh, there is limited information regarding patterns and factors associated with infections among patients receiving immunosuppressive medications. Objective The present study aimed to find out patterns and predictors associated with infection among patients who were on different immunosuppressive medications due to chronic rheumatological disease. Methodology This was a retrospective study; all confirmed cases of (new and old) different rheumatological diseases on disease-modifying agents attended at the rheumatology clinic of Dhaka Medical College Hospital from January 2019 to December 2021 were enrolled. Result Among 489 cases, 90 (18.4%) patients had documented infections. The most common rheumatological diseases were systemic lupus erythematosus (28, 31.1%), ankylosing spondylitis (26, 28.8%), and rheumatoid arthritis (20, 22.2%). COVID-19 (28, 31.1%) was the most commonly occurring infection followed by urinary tract infection (14, 15.6%), fungal infection (12, 13.3%), herpes zoster (10, 11.1%), pulmonary tuberculosis (TB) (eight, 8.8%), latent TB (seven, 7.7%), community-acquired pneumonia (six, 6.6%), and sepsis (three, 3.3%). Infection was most prevalent among patients who received steroids of more than 10 mg per day (17, 18.8%) than those less than 10 mg steroid per day (six, 6.7%), Factors associated with infections were (odds ratio, 95% CI, p-value) underweight (2.3, [1.3-2.7], 0.001), anemia (1.8, [1.1-5.7], 0.01), neutropenia (1.6, [1.1-2.9], <0.002), hypoalbuminemia (3.1, [1.6-4.9], 0.001), hypovitaminosis D (1.9, [1.3-4.5], 0.001), high blood sugar (1.5, [1.1-5.3], 0.02), inadequate counseling of steroid side effect (1.7, [1.1-3.9], 0.03), prednisolone >10mg/day (2.2, [1.19-4.10], 0.001). Conclusion COVID-19 pneumonia, urinary tract infections, fungal infection, tuberculosis, herpes zoster, and community-acquired pneumonia were commonly occurring infections among patients receiving different immunosuppressive medications. Factors like poor nutritional status, presence of anemia, leucopenia, hypoalbuminemia, hyperglycemia, and hypovitaminosis D had a significant association with infection. Moreover, inadequate counseling of steroid side effects and history of daily intake of prednisolone (>10mg/day) were also significant factors associated with infection.

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BACKGROUND: Sphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathologic damages in models of viral pneumonia.
OBJECTIVE: Is it feasible to administer an SRL therapy, here ozanimod (OZA), to acutely ill patients infected with SARS-CoV-2?
METHODS: The prospective randomized open-label COVID-19 Ozanimod Intervention (COZI) pilot trial was conducted in three Canadian hospitals. Patients admitted for COVID-19 requiring oxygen were eligible. Randomization was stratified for risk factors of poor outcome and oxygen needs at inclusion. Participants were allocated to standard of care or to standard of care plus OZA. OZA (oral, once daily, incremental dosage) was administered for a maximum of 14 days. Primary end point investigated for size effect and variance over time was the assessment of safety and efficacy, evaluated by the daily score on the World Health Organization-adapted six-point ordinal scale for clinical improvement analyzed under the intention-to-treat principle.
RESULTS: Twenty-three patients were randomized to the standard of care arm, and 20 were randomized to the OZA arm from September 2020 to February 2022. Evaluation of efficacy showed nonsignificant reductions of median (interquartile range) duration of respiratory support (6 [3-10] vs 9 [4-12] days; P = .34), median duration of hospitalization (9 [6-12] vs 10 [6-18] days; P = .20), and median time to clinical improvement (4 [3-7] vs 7 [3-11] days; P = .12) for OZA compared with standard of care, respectively. Heart rate was significantly lower with OZA (65 [ 63-67] vs 71 [69-72] beats/min; P < .0001). However, QT and PR intervals were not affected. No severe adverse drug reaction was reported.
CONCLUSIONS: To our knowledge, SRL utility in severe pneumonia has never been tested in patients. This study shows for the first time that this new pharmacologic agent may safely be administered to patients hospitalized for viral pneumonia, with potential clinical benefits. Bradycardia was frequent but well tolerated.
BACKGROUND: ClinicalTrials.gov; No.: NCT04405102; URL: www.
RESULTS: gov.

BACKGROUND: Patients with inflammatory bowel disease (IBD) treated with immunomodulators or biologic therapy are at increased risk of infections. Malnutrition and vitamin or mineral deficiencies are common among patients with IBD. The results of various studies have indicate that vitamin deficiencies might increase the risk of infections. To evaluate the efficacy of a multivitamin and mineral supplement on the incidence of infections in patients with IBD treated with immunomodulators, biologic therapy, or combination therapy.
METHODS: This was a single-center, randomized, double-blind, placebo-controlled clinical trial to compare a multivitamin and mineral supplement (supplemented group) vs identical-in-appearance placebo (placebo group) in a total of 320 non-vitamin-deficient patients with IBD (Crohn\'s disease or ulcerative colitis) in remission with immunomodulators, biologic therapy, or combination therapy. Participants were asked to take a daily multivitamin and mineral supplement or placebo and report the occurrence of infections during a 24-week period of follow-up.
RESULTS: Treatment arms consisted of 162 and 158 patients for the supplement and placebo, respectively. In both treatment groups, 107 patients reported an infection during the 24-week follow-up period (unadjusted odds ratio, 0.93; 95% confidence interval, 0.56-1.48). In the supplemented group, 32 patients received antibiotics for an infection compared with 21 patients in the placebo group (unadjusted odds ratio, 1.61; 95% confidence interval, 0.88-2.93).
CONCLUSIONS: An over-the-counter multivitamin and mineral supplement did not reduce the risk of infection for patients with IBD in remission with immunomodulators, biologic therapy, or combination therapy.
Patients with inflammatory bowel disease are at increased risk of infections due to vitamin or mineral deficiencies. An over-the-counter supplement did not reduce the risk of infection for patients with inflammatory bowel disease in remission with immunomodulators and/or biologic therapy.

OBJECTIVE: Combination therapy with an immunomodulator (IMM) and an anti-TNF is commonly recommended in Crohn\'s disease (CD) and ulcerative colitis (UC) patients. However, little is known about relapse rates after therapeutic de-escalation. This study aimed to evaluate the risk of relapse in a cohort of UC and CD patients with long-standing clinical remission after discontinuation of IMM or anti-TNF and to identify predictive factors for relapse.
METHODS: This retrospective study included patients with UC or CD on combination therapy and clinical remission for at least 6 months. IMM or anti-TNF was stopped upon physician decision. Primary objective was to evaluate the relapse rates after discontinuation of IMM or anti-TNF and to analyze predictors of relapse.
RESULTS: The study included 88 patients, 48 patients (54.5%) discontinued IMM and 40 (45.5%) anti-TNF. During follow-up, relapse rates were 16.7% and 52.5% in the IMM discontinuation group and anti-TNF discontinuation group, respectively (p<0.001). Multivariate analysis showed that anti-TNF discontinuation (HR=3.01; 95% CI=1.22-7.43) and ileal CD location (HR=2.36; 95% CI=1.02-5.47) were predictive factors for relapse while inflammatory CD phenotype was a protective factor (HR=0.32; 95% CI=0.11-0.90). Reintroduction of anti-TNF upon relapse was effective and safe.
CONCLUSIONS: Anti-TNF discontinuation led to significantly higher relapse rates compared to IMM discontinuation in UC and CD patients on combination therapy. Anti-TNF discontinuation and ileal CD location were identified as predictive factors for relapse while inflammatory CD phenotype was a protective factor. Retreatment after anti-TNF discontinuation was effective and safe.

OBJECTIVE: Few population-based studies have investigated long-term surgery rates for Crohn\'s disease [CD]. Our aim was to analyse disease progression and surgery rates in a population-based cohort over different therapeutic eras, based on the time of diagnosis: cohort-A [1977-1995], cohort-B [1996-2008], and cohort-C [2009-2018].
METHODS: A total of 946 incident CD patients were analysed (male/female: 496/450; median age at diagnosis: 28 years [y]; interquartile range [IQR]: 22-40]). Patient inclusion lasted between 1977 and 2018. Immunomodulators have become widespread in Hungary since the mid-1990s and biologic therapies since 2008. Patients were followed prospectively, with both in-hospital and outpatient records reviewed regularly.
RESULTS: The probability of disease behaviour progression from inflammatory [B1] to stenosing or penetrating phenotype [B2/B3] significantly decreased (27.1 ± 5.3%/21.5 ± 2.5%/11.3 ± 2.2% in cohorts A/B/C, respectively, after 5 years; 44.3 ± 5.9%/30.6 ± 2.8%/16.1 ± 2.9% after 10 years, respectively; [pLogRank <0.001]). The probability of first resective surgery between cohorts A/B/C were 33.3 ± 3.8%/26.5 ± 2.1%/28.1 ± 2.4%, respectively, after 5 years; 46.1 ± 4.1%/32.6 ± 2.2%/33.0 ± 2.7% after 10 years, respectively; and 59.1 ± 4.0%/41.4 ± 2.6% [cohorts A/B] after 20 years. There was a significant decrease in first resective surgery risk between cohorts A and B [plog rank = 0.002]; however, no further decrease between cohorts B and C [plog rank = 0.665]. The cumulative probability of re-resection in cohorts A/B/C was decreasing over time (17.3 ± 4.1%/12.6 ± 2.6%/4.7 ± 2.0%, respectively, after 5 years [plog rank = 0.001]).
CONCLUSIONS: We report a continuous decline in reoperation rates and disease behaviour progression in CD over time, with the lowest values in the biologic era. In contrast, there was no further decrease in the probability of first major resective surgery after the immunosuppressive era.

OBJECTIVE: Scepticism about the efficacy of thiopurines for ulcerative colitis [UC] is rising. This study aimed to evaluate mercaptopurine treatment for UC.
METHODS: In this prospective, randomized, double-blind, placebo-controlled trial, patients with active UC, despite treatment with 5-aminosalicylates [5-ASA], were randomized for therapeutic drug monitoring [TDM]-guided mercaptopurine treatment or placebo for 52 weeks. Corticosteroids were given in the first 8 weeks and 5-ASA was continued. Proactive metabolite-based mercaptopurine and placebo dose adjustments were applied from week 6 onwards by unblinded clinicians. The primary endpoint was corticosteroid-free clinical remission and endoscopic improvement [total Mayo score ≤2 points and no item >1] at week 52 in an intention-to-treat analysis.
RESULTS: Between December 2016 and April 2021, 70 patients were screened and 59 were randomized at six centres. In the mercaptopurine group, 16/29 [55.2%] patients completed the 52-week study, compared to 13/30 [43.3%] on placebo. The primary endpoint was achieved by 14/29 [48.3%] patients on mercaptopurine and 3/30 [10%] receiving placebo (Δ = 38.3%, 95% confidence interval [CI] 17.1-59.4, p = 0.002). Adverse events occurred more frequently with mercaptopurine [808.8 per 100 patient-years] compared to placebo [501.4 per 100 patient-years]. Five serious adverse events occurred, four on mercaptopurine and one on placebo. TDM-based dose adjustments were executed in 22/29 [75.9%] patients, leading to lower mercaptopurine doses at week 52 compared to baseline.
CONCLUSIONS: Optimized mercaptopurine treatment was superior to placebo in achieving clinical, endoscopic and histological outcomes at 1 year following corticosteroid induction treatment in UC patients. More adverse events occurred in the mercaptopurine group.