Tofacitinib and Baricitinib in Type 2 Diabetic Patients with Rheumatoid Arthritis.

Background and Objectives: Recently, a randomized controlled trial suggested a potential benefit of baricitinib in patients with diabetes mellitus, preserving ß-cell function. However, the clinical evidence currently available is limited. We aimed to assess the potential impact of tofacitinib and baricitinib on type 2 diabetes mellitus (T2DM) patients with rheumatoid arthritis. Materials and Methods: The candidates for this observational, retrospective, single-center study were selected from a cohort of 120 rheumatoid arthritis patients treated with tofacitinib or baricitinib between September 2017 and September 2023. The eligibility criteria included patients with T2DM who were receiving oral antidiabetic drugs (OADs). The primary outcome was the glycosylated hemoglobin (HbA1c) value after 6 months of a JAK inhibitor treatment. Secondary outcomes included body mass index (BMI) and rheumatoid arthritis disease activity. Differences were evaluated using Fisher's exact test, as well as the Mann-Whitney test or the Wilcoxon test. Results: Thirteen patients were included; 46.2% (6/13) underwent treatment with tofacitinib, while 53.8% (7/13) were treated with baricitinib. At 6 months, baricitinib treatment resulted in a reduction in HbA1c (p = 0.035), with 57.1% (4/7) of patients achieving values <7%, and 28.6% (2/7) of patients requiring a reduction in OAD dosage. Concerning BMI, an increase (p = 0.022) was observed at 6 months following baricitinib administration. All the patients treated with either tofacitinib or baricitinib achieved remission or low disease activity, without requiring statistically significant changes in concomitant rheumatoid arthritis treatment. Conclusions: In T2DM patients with rheumatoid arthritis, baricitinib can improve insulin sensitivity and glucose uptake, enabling the optimization of T2DM management.

Are There Sex-Related Differences in the Effectiveness of Janus Kinase Inhibitors in Rheumatoid Arthritis Patients?

Background: There is evidence suggesting the existence of sex differences in the effectiveness of specific drug classes for rheumatoid arthritis (RA). Our study stands as the first to elucidate sex-related differences in the effectiveness of Janus kinase (JAK) inhibitors. Methods: The study involved 150 RA patients treated with tofacitinib, baricitinib, upadacitinib, or filgotinib between September 2017 and October 2023. Sex differences in achieving remission and low disease activity (LDA) were identified through logistic regression analyses. Sex disparities in treatment effectiveness survival were evaluated through the Kaplan-Meier estimate, employing the log-rank test for comparison. The Cox model was applied to analyze the variable sex as a potential factor that could influence the maintenance of the JAK inhibitor treatment effectiveness. Results: Concerning the achievement of remission and LDA, no differences were observed between sexes in terms of the 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). With respect to the DAS28-erythrocyte sedimentation rate (ESR), female patients, compared to males, possessed 70% lower odds of achieving remission (p = 0.018) and 66% lower odds of achieving LDA (p = 0.023). No differences were observed in treatment effectiveness survival between sexes (p = 0.703). Sex was not found to influence the survival of JAK inhibitor treatment effectiveness (p = 0.704). Conclusions: Being a female or male patient does not entail differences in the effectiveness of the JAK inhibitor treatment. Our findings encourage the consideration of a global pool of composite indices (DAS28-ESR/CRP, CDAI, SDAI) to measure RA disease activity, thus individualizing the target value as advocated by the treat-to-target strategy.

Patient-related factors influencing the effectiveness and safety of Janus Kinase inhibitors in rheumatoid arthritis: a real-world study.

In real-world scenarios, Janus Kinase (JAK) inhibitors are often offered to "difficult-to-treat" rheumatoid arthritis patients, quite different from those included in randomized controlled trials. Our study aimed to evaluate the influence of patient-related factors on the effectiveness and safety of JAK inhibitors in real-world clinical practice. This observational retrospective study involved rheumatoid arthritis patients who received treatment with either tofacitinib, baricitinib, upadacitinib, or filgotinib. At 12 months of treatment, reasons for and rates of JAK inhibitor treatment discontinuation were examined. Treatment retentions were analyzed through Cox proportional hazard regression models and Kaplan-Meier estimates. Patient-related factors that could influence treatment retention were evaluated for the discontinuation reasons of lack of effectiveness and adverse events. At 12 months of treatment, discontinuation rates for 189 JAK inhibitor treatments were: lack of effectiveness (24.3%), adverse events (20.6%), and other reasons (3.7%). The remaining 51.4% represents the treatment continuation rate. No patient-related factors evaluated had an influence on treatment discontinuation due to lack of effectiveness. Ae significantly increased the risk of treatment discontinuation due to adverse events (p = 0.030). In terms of age, at 12 month of treatment, discontinuation rates due to adverse events were: < 65 years, 14.4% vs. 65 years or older, 26.3% (p = 0.019). Rheumatoid arthritis patients aged 65 years or older showed an increased risk of JAK inhibitor treatment discontinuation due to adverse events. Factors not related to treatment discontinuation were: sex, rheumatoid arthritis disease duration, rheumatoid arthritis disease activity, seropositivity for rheumatoid factor, seropositivity for anti-cyclic citrullinated peptides, number of prior biologic treatments, number of prior JAK inhibitor treatments, concomitant use of glucocorticoids, and concomitant use of conventional synthetic disease-modifying antirheumatic drugs.

Adverse reactions to Janus kinase inhibitors: Study of their incidence and predictive factors in patients with rheumatoid arthritis. / Reacciones adversas a inhibidores de quinasa Janus: estudio de su incidencia y de factores predictivos en los pacientes con artritis reumatoide.

BACKGROUND AND OBJECTIVE: The safety profile of Janus Kinase (JAK) inhibitors has acquired attention due to post-marketing observed adverse drug reactions. The study focuses on the analysis of adverse reactions related to tofacitinib, baricitinib, upadacitinib, and filgotinib in rheumatoid arthritis patients, including identifying predictive factors linked to their occurrence. PATIENTS AND METHODS: Observational retrospective study. Adult patients with rheumatoid arthritis from a university hospital receiving JAK inhibitor treatment between September 2017 and January 2024 were included. The cumulative incidence of each adverse reaction was calculated using the Naranjo scale. Risk factors for developing adverse reactions were identified through logistic regression analyses. RESULTS: Two hundred twenty-three patients were included, with 28.7% presenting adverse reaction related to JAK inhibitor treatment. The adverse drug reactions with the highest cumulative incidence were infections and gastrointestinal disorders. Infections included: upper respiratory tract (4.5%), cellulitis (3.1%), urinary tract (2.7%), herpes zoster (1.8%). Gastrointestinal disorders comprised: abdominal pain (4.0%), diarrhea (3.6%), nausea and vomiting (3.6%), gastrointestinal perforation (1.3%), diverticulitis (0.9%). Classified at 0.5% were: headache, paresthesias, skin rash, severe neutropenia, insomnia, dyspnea, hypertensive crisis. As risk factors, were identified: the treatment with a non-selective JAK inhibitor (OR adjusted: 4.03; 95% CI: 1.15-14.10; P=.029) and older age (OR adjusted: 1.03; 95% CI: 1.00-1.05; P=.036). CONCLUSIONS: Infections and gastrointestinal disorders represented the adverse reactions related to JAK inhibitor treatment with the highest cumulative incidence, with risk factors for their occurrence being non-selective JAK inhibitor treatment and older age of the patient.

Optimization of a home hospitalization program for hematopoietic stem cell transplantation with ehealth integration and clinical pharmacist involvement.

Home hospitalization represents an alternative to traditional hospitalization, providing comparable clinical safety for hematological patients. At-home therapies can range from the delivery of intravenous antibiotics to more complex scenarios, such as the care during the early period after hematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy. Early discharge from conventional hospitalization is feasible and helps reduce hospital resources and waiting lists. The coordinated efforts of multidisciplinary teams, including hematologists, nurses, and pharmacists, ensure patient safety and continuity of care. The traditional model of home hospitalization relies on home visits and telephone consultations with physicians and nurses. However, the use of eHealth technologies, such as MY-Medula, can enhance communication and monitoring, and thereby improve patient outcomes with no additional costs. The active involvement of a clinical pharmacist in home hospitalization programs is essential, not only for the proper logistical management of the medication but also to ensure its appropriateness, optimize treatment, address queries from the team and patients, and promote adherence. In conclusion, the implementation of hematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy home hospitalization programs that use both an eHealth tool and a multidisciplinary care model can optimize patient care and improve quality of life without increasing healthcare costs.

Impact of bread diet on intestinal dysbiosis and irritable bowel syndrome symptoms in quiescent ulcerative colitis: A pilot study.

Gut microbiota may be involved in the presence of irritable bowel syndrome (IBS)-like symptomatology in ulcerative colitis (UC) patients in remission. Bread is an important source of dietary fiber, and a potential prebiotic. To assess the effect of a bread baked using traditional elaboration, in comparison with using modern elaboration procedures, in changing the gut microbiota and relieving IBS-like symptoms in patients with quiescent ulcerative colitis. Thirty-one UC patients in remission with IBS-like symptoms were randomly assigned to a dietary intervention with 200 g/d of either treatment or control bread for 8 weeks. Clinical symptomatology was tested using questionnaires and inflammatory parameters. Changes in fecal microbiota composition were assessed by high-throughput sequencing of the 16S rRNA gene. A decrease in IBS-like symptomatology was observed after both the treatment and control bread interventions as reductions in IBS-Symptom Severity Score values (p-value < 0.001) and presence of abdominal pain (p-value < 0.001). The treatment bread suggestively reduced the Firmicutes/Bacteroidetes ratio (p-value = 0.058). In addition, the Firmicutes/Bacteroidetes ratio seemed to be associated with improving IBS-like symptoms as suggested by a slight decrease in patient without abdominal pain (p-value = 0.059). No statistically significant differential abundances were found at any taxonomic level. The intake of a bread baked using traditional elaboration decreased the Firmicutes/Bacteroidetes ratio, which seemed to be associated with improving IBS-like symptoms in quiescent ulcerative colitis patients. These findings suggest that the traditional bread elaboration has a potential prebiotic effect improving gut health (ClinicalTrials.gov ID number of study: NCT05656391).

Exploring the Associations of Inflammatory and Oxidative Stress Biomarkers with Pancreatic Diseases: An Observational and Mendelian Randomisation Study.

Identifying biomarkers linked to pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) is crucial for early detection, treatment, and prevention. Methods: Association analyses of 10 serological biomarkers involved in cell signalling (IFN-γ, IL-6, IL-8, IL-10), oxidative stress (superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities, total glutathione (GSH), malondialdehyde (MDA) levels), and intestinal permeability proteins (zonulin, I-FABP2) were conducted across PDAC (n = 12), CP (n = 21) and control subjects (n = 23). A Mendelian randomisation (MR) approach was used to assess causality of the identified significant associations in two large genetic cohorts (FinnGen and UK Biobank). Results: Observational results showed a downregulation of SOD and GPx antioxidant enzyme activities in PDAC and CP patients, respectively, and higher MDA levels in CP patients. Logistic regression models revealed significant associations between CP and SOD activity (OR = 0.21, 95% CI [0.05, 0.89], per SD), GPx activity (OR = 0.28, 95% CI [0.10, 0.79], per SD), and MDA levels (OR = 2.05, 95% CI [1.36, 3.08], per SD). MR analyses, however, did not support causality. Conclusions: These findings would not support oxidative stress-related biomarkers as potential targets for pancreatic diseases prevention. Yet, further research is encouraged to assess their viability as non-invasive tools for early diagnosis, particularly in pre-diagnostic CP populations.