Introduction

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a disease that complements Nonalcoholic Fatty Liver Disease (NAFLD) and is newly defined in 2020. It is defined based on metabolic abnormalities, regardless of the presence of liver disease caused by other causes such as alcohol consumption. Regarding the newly defined MAFLD, there has not been many studies related to the prevalence and risk factors in Korea, and no studies were found targeting soldiers, especially pilots.

Aims & Methods

The purpose of this study is to identify prevalence and risk factors for MAFLD in Korean air force army inclusive of pilots. The subjects are 1044 soldiers who underwent health checkups in Korean Air Force Aerospace medical center from January 2020 to December 2022. The data was retrospectively collected including age, height, weight, body mass index, waist circumference, blood pressure, smoking, drinking, exercise intensity, various blood test results, presence of fatty liver, and degree of fatty liver. Risk factors were analyzed using logistic regression.

Results

There were 667 pilots (64%) in our study, of whom 477 (72%) were high-performing pilots. The prevalence of MAFLD was 316 (30%) in all soldier. There was difference in the prevalence of MAFLD between pilot and non-pilot group (pilot group: 185 (28%), non-pilot group: 131 (35%) p-value=0.018). According to the multivariate analysis, body mass index (BMI), diabetes, systolic blood pressure, triglycerides (TG), uric acid (UA), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), alanine aminotransferase (ALT) were a risk factor associated with MAFLD among the entire soldiers. When categorized into pilot and non-pilot group, risk factors were associated with BMI, diabetes, alcohol consumption, and ALT in the non-pilot group. In the pilot group, they were statistically associated with age, BMI, dyslipidemia, TG, UA, HDL and ALT. Among them, UA showed the largest difference between the non-pilot group and the test group (non-pilot group: 1.14 (95% CI: 0.80-1.62), pilot group: 1.80 (95% CI: 1.38-2.36)).

Conclusion

There was a difference in the prevalence of MAFLD between pilot and non-pilot group. In particular, UA could be used to predict MAFLD as a specific risk factor in pilots comparing with non-pilots.

Introduction

Upadacitinib, a selective JAK inhibitor, is approved for moderate-to-severe Crohn’s disease (CD). However, real-world data on its effectiveness and safety, particularly in highly refractory populations, remain scarce. The UPITA-Crohn registry was established to evaluate the outcomes of upadacitinib in clinical practice across multiple centers in Andalusia, Spain.

Aims & Methods

This ambispective, multicenter registry included 142 patients with refractory CD treated with upadacitinib in 12 Andalusian hospitals. Clinical and biochemical data were collected at baseline, weeks 12 and 16, and at 6 months. Clinical remission (CR) was defined as a Harvey-Bradshaw Index (HBI) <5; clinical-biochemical remission (CBR) as HBI <5, CRP <5 mg/L, and fecal calprotectin <250 μg/g; and steroid-free remission (SFR) as HBI <5 without corticosteroids from week 12. Outcomes were also analyzed overall and according to prior exposure to advanced therapies.

Results

The UPITA-Crohn registry cohort included 142 patients with refractory Crohn’s disease. The mean age was 40.8 years (range 18–76), with 40% male. The mean disease duration at the time of upadacitinib initiation was 13.3 years (range 1–42), with a mean of 2.7 failed advanced therapies, highlighting a population with longstanding and complex disease. Most patients had ileocolonic involvement (50%), 22% had perianal disease, and 32% had previously undergone resective surgery.
The majority (74.4%) received induction with upadacitinib 45 mg for 12 weeks. At week 12, clinical remission was achieved by 54% of patients, with 15% reaching clinical-biochemical remission. At 6 months, among those still on treatment, 48.3% maintained clinical remission, 16.1% achieved clinical-biochemical remission, and 18.4% achieved steroid-free remission (Table 1).
When stratified by prior therapy, 6-month clinical remission was similar between patients with ≥2 prior advanced therapies (48.5%) and those with only 1 prior therapy (47.4%), with no significant difference. Steroid-free and clinical-biochemical remission rates were also slightly higher among less refractory patients, but differences were modest.
A total of 31 patients (21.8%) discontinued upadacitinib before 6 months, mainly due to primary non-response (70.9%). Adverse events were reported in 21.1% of patients, most commonly infections (9 cases), acne (7), transient transaminase elevation (5), and herpes zoster (2). Seven discontinuations were due to serious adverse events, including thrombosis, stroke, myocardial infarction, fever, and severe infections.

Table 1: Effectiveness Outcomes

Conclusion

Upadacitinib demonstrated meaningful effectiveness and a manageable safety profile in a real-world cohort of refractory Crohn’s disease patients. Notably, clinical remission rates remained stable even in those with multiple prior advanced therapies, suggesting upadacitinib may be a valuable option for patients with limited alternatives.

Introduction

The need for effective therapies in moderate to severe Crohn's disease (CD) drives the comparative evaluation of biologic treatments. The current work uses an anchored Matching-Adjusted Indirect Comparison (MAIC) to assess the efficacy of guselkumab (GUS) relative to risankizumab (RZB) during the treatment induction phase. This MAIC is using data from five phase 3 placebo-controlled blinded clinical trials (GRAVITI, GALAXI 2, GALAXI 3, ADVANCE, MOTIVATE).

Aims & Methods

Adult patients with moderate to severe CD, as defined in GRAVITI, GALAXI 2/3, ADVANCE and MOTIVATE trials were included. An anchored MAIC was utilized, leveraging placebo as common comparator and following guidance from the National Institute for Health Care Excellence in UK. The analysis aligned pooled individual patient data for GUS with published data for RZB by matching exclusion criteria and patient baseline characteristics that could be treatment effect modifiers (eg Age, Sex, BMI, CDAI, disease location or prior biologic treatment failure). During induction, patients received GUS 200 mg intravenous or 400 mg subcutaneous at weeks 0, 4, and 8 or RZB 600 mg intravenous at weeks 0, 4, and 8. The endpoints of interest were symptomatic endpoints such as clinical remission, PRO-2 remission, clinical response, abdominal pain and stool frequency remission, as well as endoscopic response at week 12, which marks the end of the induction period.

Results

After matching, baseline characteristics were balanced between the GUS and RZB cohorts. In a mixed population of bio-naïve and bio-experienced patients, GUS demonstrated statistically significant results in comparison to RZB for PRO-2 remission, clinical response and abdominal pain remission (table 1). Clinical remission showed a trend in favor of GUS, endoscopic response and stool frequence remission were comparable to RZB. In patients with biologic treatment failure versus the MOTIVATE trial, results had been generally more in favor of GUS, while maintaining positive outcomes seen across mixed populations (ADVANCE & MOTIVATE). Results were also mostly consistent whether analyzing pooled GUS data or individual trials, eg from GRAVITI, against RZB.

Table 1: Results of GUS from pooled GRAVITI, GALAXI 2/3 vs. RZB for induction period at week 12

Conclusion

The anchored MAIC analysis demonstrates comparable to even superior efficacy of guselkumab over risankizumab in inducing symptomatic improvements in Crohn's disease patients. It also suggests that subcutaneous induction seems to be preferential over iv induction.

Disclosure

van Sanden S, Trevisan M, Strobl A and Wirth D are employees of J&J Innovative Medicines

Introduction

Inflammatory Bowel Disease (IBD), including Ulcerative Colitis (UC) and Crohn's Disease (CD), is a chronic gastrointestinal disorder marked by progressive inflammation. Recent therapies focus on a treat-to-target (T2T) strategy, as per STRIDE-II guidelines, aiming for defined short-term, intermediate-term, and long-term goals. While Western countries favor a top-down approach, emerging nations still largely follow the step-up method. Our study assesses the real-world effectiveness of the step-up strategy in meeting these targets at a tertiary care hospital in South India.

Aims & Methods

To study the short-term, intermediate-term and long-term treat-to-target goals (as per STRIDE-II recommendations) met, based on the current medical therapy in cases of Ulcerative Colitis and Crohn’s disease in a real world setting.
This study included 122 IBD patients (61 UC, 61 CD) treated with step-up approach of medical therapy over 18 months. Targets assessed included clinical response (short-term) at 4-8 weeks, biomarker normalization and clinical remission (intermediate-term) at 3 months, endoscopic remission and improvement in quality of life (long-term) at 6-9 months. Data on patient demographics, disease characteristics, therapeutic regimens, and adverse events were analysed using statistical methods.

Results

Short-term clinical response was achieved in 91.8% of UC patients and 86.9% of CD patients. Clinical remission was seen in 80.3% of UC and 70.5% of CD cases at 3 months. Biomarker normalisation was seen in 78.68% of UC and 68.85% of CD patients. Mucosal healing was observed in 31.2% of UC and 36.1% of CD patients at 6-9 months. Quality of life goals were met by 66% of UC and 67% of CD patients. Deep remission (clinical along with endoscopic remission) was achieved in 29.5% of UC and 32.8% of CD cases. Biologics and non-biologics showed no significant difference in achieving therapy goals. Baseline severity impacted outcomes, with severe UC patients struggling more to meet both short-term and long-term targets compared to those with milder forms (p<0.05). Similarly, mild and moderate CD patients achieved clinical remission better than severe CD patients (p<0.05). Multivariate analysis with logistical regression showed that in Crohn’s disease, baseline CDAI score predicted the likelihood of clinical remission (p=0.011). Baseline SES-CD score predicted the likelihood of achieving mucosal healing (p=0.045). Colonic CD was more likely to achieve mucosal healing than other sub-types (p=0.02). Sub-group analysis showed that elderly and pediatric populations, did not show statistically significant variations in treatment success.

Conclusion

Findings from our study suggest that the step-up approach can achieve outcomes that are broadly comparable to those reported in top-down studies from Western settings. While the top-down strategy is traditionally associated with early disease control, our results highlight that a carefully monitored and timely step-up approach can also be effective, particularly in real-world, resource-limited environments. These insights support the need for individualised treatment strategies that consider both disease severity and contextual healthcare factors.

References

Disclosure

Nil