Minoru Matsuura

Background and Aims: Multiple advanced therapies are available for the treatment of Crohn’s disease (CD). Treatment patterns in newly diagnosed patients and the factors associated with persistence remain unclear. We present interim results of the iCREST-CD registry describing treatment patterns and persistence with advanced therapies. Methods: Patients aged ≥16 years with newly diagnosed CD and who had no prior exposure to advanced therapies were enrolled. Persistence of advanced therapies was estimated using Kaplan–Meier analyses, and associated factors were identified using multivariable Cox proportional hazards models. Persistence was also compared between patients who initiated therapy early or later after diagnosis. Results: Of 672 patients (68.2% male; mean age 29.4 ± 13.1 years), 498 (74.1%) initiated advanced therapy: infliximab (IFX; 121), adalimumab (ADA; 244), ustekinumab (UST; 107), or vedolizumab (VDZ; 26). Advanced therapy was initiated within 1 year of diagnosis in 404 (60.1%). The 36-month treatment persistence rates for IFX, ADA, UST, and VDZ were 77.5%, 75.7%, 79.8%, and 49.0%, respectively. After propensity score adjustment using inverse probability of treatment weighting, the early initiation was associated with greater persistence than delayed initiation, although the difference did not reach statistical significance (hazard ratio, 0.61; 95% confidence interval, 0.35-1.09; P = .067). Conclusions: A high prevalence of early advanced therapy use and a high level of persistence with first-line advanced therapy were identified in this national cohort. Early initiation was associated with greater treatment persistence than delayed initiation, suggesting the potential clinical relevance of earlier advanced therapy use in routine practice. These findings require confirmation in other prospective studies aiming to evaluate early intervention strategies. Registration: The study was registered with the University Hospital Medical Information Network Clinical Trials Registry (umin.ac.jp/ctr Identifier: UMIN000032237) prior to initiation.

Post-marketing surveillance of tofacitinib in patients with ulcerative colitis in Japan: a post hoc analysis of safety and effectiveness in older (≥65 years) and younger (<65 years) patients

Background/Aims: Vedolizumab (VDZ), a gut-selective monoclonal antibody for ulcerative colitis (UC) treatment, has no established biomarkers or clinical features that predict long-term remission. Week 2 remission, a potential predictor of long-term remission, could inform maintenance treatment strategy. Methods: This retrospective, observational chart review included patients with UC in Japan who initiated VDZ between December 2018 and February 2020. Outcome measures included 14- and 54-week remission rates in patients with week 2 and non-week 2 remission (remission by week 14), 54-week remission rates in patients with week 14 remission and primary nonresponse, and predictive factors of week 2 and week 54 remission (logistic regression). Results: Overall, 332 patients with UC (176 biologic-naïve and 156 biologic-non-naïve) were included. Significantly more biologic-naïve than biologic-non-naïve patients achieved week 2 remission (36.9% vs. 28.2%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.05–1.94; P= 0.0224). Week 54 remission rates were significantly different between week 14 remission and primary nonresponse (both groups: P< 0.0001), and between week 2 and non-week 2 remission (all patients: OR, 2.41; 95% CI, 1.30–4.48; P= 0.0052; biologic-naïve patients: OR, 2.40; 95% CI, 1.10–5.24; P= 0.0280). Week 2 remission predictors were male sex, no anti-tumor necrosis factor alpha exposure, and normal/mild endoscopic findings. Week 54 remission was significantly associated with week 2 remission and no tacrolimus use. Conclusions: Week 2 remission with VDZ is a predictor of week 54 remission in patients with UC. Week 2 may be used as an evaluation point for UC treatment decisions. (Japanese Registry of Clinical Trials: jRCT-1080225363)

Background/Aims: Previous literature suggests that the response of patients with ulcerative colitis to vedolizumab may be affected by previous biologic therapy exposure. This real-world study evaluated vedolizumab treatment effectiveness in biologicnon-naïve patients. Methods: This was a multicenter, retrospective, observational chart review of records from 16 hospitals in Japan (December 1, 2018, to February 29, 2020). Included patients who had ulcerative colitis, were aged ≥ 20 years, and received at least 1 dose of vedolizumab. Outcomes included clinical remission rates from weeks 2 to 54 according to prior biologic exposure status and factors associated with clinical remission up to week 54. Results: A total of 370 eligible patients were included. Clinical remission rates were significantly higher in biologic-naïve (n=197) than in biologic-non-naïve (n=173) patients for weeks 2 to 54 of vedolizumab treatment. Higher clinical remission rates up to week 54 were significantly associated with lower disease severity (partial Mayo score ≤ 4, P= 0.001; albumin ≥ 3.0, P= 0.019) and the duration of prior anti-tumor necrosis factor α (anti-TNFα) therapy (P= 0.026). Patients with anti-TNFα therapy durations of < 3 months, 3 to < 12 months, and ≥ 12 months had clinical remission rates of 28.1%, 32.7%, and 60.0%, respectively (P= 0.001 across groups). Conclusions: The effectiveness of vedolizumab in biologic-non-naïve patients was significantly influenced by duration of prior anti-TNFα therapy. (Japanese Registry of Clinical Trials: jRCT-1080225363)

Transabdominal intestinal ultrasound (IUS) is a promising, non-invasive tool for monitoring ulcerative colitis (UC). This modality has the advantage of assessing intestinal inflammation transmurally, suggesting that UC can be considered a transmural disease. Determining what transabdominal IUS findings indicate in terms of histopathology would improve its value in assessing disease activity. However, associations between sonographic and histopathological findings have not yet been established for active UC. To address this gap, we investigated patients with active UC who underwent colectomy following IUS examination. Patients who underwent total colectomy for severe active UC within 1 week of undergoing transabdominal IUS at our facility between December 2020 and March 2023 were consecutively included in this study. Sonographic and histopathological findings were compared for each colonic segment in these patients. Four patients underwent IUS 3-6 days before colectomy, which was performed due to insufficient response to medical treatment. IUS findings, particularly loss of bowel stratification and increased color Doppler signals, were associated with severe inflammation and vascular proliferation in the transmural colon, including the subserosa. Thickened muscularis propria was also observed in inflamed colonic segments; this may have contributed to the increased bowel wall thickness according to IUS. This is the first report comparing IUS findings and transmural pathological features in active UC. It provides an imaging atlas and clinical insights into the role of IUS in determining transmural histopathological inflammatory status in patients with active UC.

Background/Aims: Crohn’s disease (CD) leads to bowel damage and disability if suboptimally treated. We investigated firstyear treatment decisions and real-world use of biologics in patients with CD in Japan. Methods: In this retrospective observational study (2010–2021) from the JMDC claims database, patients with a new diagnosis of CD (no CD claims record within 12 months before index) who received ≥ 1 pre-defined treatment were grouped by use of biologics and systemic corticosteroids (SCS) within the first year of diagnosis. Results: Of 823 patients included, 470 (57.1%) were prescribed biologics and 353 (42.9%) were not; 77.6% were male, 75.7% had adult-onset CD, and median age was 24 years. Patients prescribed biologics were younger (median: 23 years vs. 28 years) and more had perianal lesions (43.0% vs. 22.9%) than those not prescribed biologics; 64.9% (95% confidence interval, 60.4%–69.2%) received a top-down treatment approach (no SCS before biologics). Factors significantly associated with a top-down treatment approach were male sex, perianal lesions, no use of immunomodulators, and use of anti-tumor necrosis factor therapies. The proportion of patients receiving SCS before biologics (step-up approach) increased after 2018, with a shift from prednisolone to budesonide from 2016. Persistence with first biologics decreased over time, with no differences between biologic types. Conclusions: Use of biologics for treatment of CD within the first year of diagnosis in Japan has remained stable over the past decade. However, there was a shift to a step-up treatment approach, with an increase in use of SCS before biologics over time.

Background/Aims: The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response. Methods: In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled. Results: Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00–7.62; P= 0.050) and shorter disease duration (OR for median duration ≥ 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13–0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response. Conclusions: Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence.

Background/Aims: A previous health insurance claims study of Japanese patients with newly diagnosed Crohn’s disease (CD) reported an increase in “step-up” approach from 2010 to 2020, with biologic use in the first year remaining stable. This study examined systemic corticosteroid (SCS) use for newly diagnosed CD in Japan and compared patients who were escalated (“step-up”) and were not escalated to biologics.Methods: This retrospective longitudinal cohort study used health insurance claims data (JMDC database). Patients diagnosed with CD from 2010 to 2020 who had no CD-related claims for ≥ 1 year before index, were traceable for ≥ 1 year after index, and treated with ≥ 1 pre-defined treatment were included. Patients classified by SCS and/or biologic use within 1 year after diagnosis were compared.Results: Of 823 patients, 379 (46.1%) received SCS in the first year; of these, 43.5% escalated to biologics (step-up group) and 56.5% did not (SCS group). The proportion of patients receiving SCS increased from 25.8% in 2010–2011 to 55.5% in 2020; proportion escalated to biologics increased from 33.8% in 2016–2017 to 51.0% in 2020. The step-up group was significantly younger, more likely to have perianal lesions, and received more intensive treatments than the SCS group. In terms of SCS use, the step-up group was more likely to have shorter time-to-SCS initiation, and a higher initial SCS dose, than the SCS group.Conclusions: Escalation from SCS to biologics in Japanese patients with newly diagnosed CD increased between 2016 and 2020, particularly in patients with younger onset CD or perianal complications.

Background The prevalence and characteristics of inflammatory bowel disease-associated spondyloarthritis (IBD-SpA) in Japan are unclear. Moreover, methods for screening SpA among IBD patients have not been established. Methods This single-center prospective multidisciplinary study included consecutive patients with IBD, which was newly diagnosed within the past 3 years (early IBD). Board-certified rheumatologists examined the patients for disease history and musculoskeletal manifestations, with imaging studies if needed. Questionnaires assessed patient-reported outcomes and Psoriatic Arthritis Screening and Evaluation (PASE) scores. Results We identified 85 eligible patients with early IBD, 22 (25.9%) of whom had Crohn’s disease, 63 (74.1%) had ulcerative colitis, and 3 (3.5%) had IBD-SpA diagnosed prior to study enrollment. Rheumatologist evaluations identified additional seven SpA cases, resulting in a total of 10 patients (11.8%) with IBD-SpA (1: axial, 9: peripheral). IBD patients without SpA often presented with back pain (52%) and peripheral joint pain (24%), whereas arthritis, cervical and thoracic pain, and inflammatory back pain were more frequent in IBD-SpA. Newly identified IBD-SpA cases tended to have lower-limb arthritis, dactylitis, and enthesitis, compared with previously diagnosed IBD-SpA cases. For patients with active SpA symptoms in the past 6 months, PASE demonstrated that the area under the receiver operating characteristic curve was 0.87 (95% confidence interval: 0.68, 1.00). The optimal cut-off (33 points) had a sensitivity of 0.88 and specificity of 0.88. Conclusions This prospective study found rheumatologist evaluation increased SpA diagnosis and 11.8% of Japanese early IBD patients had IBD-SpA. PASE questionnaires may be effective for screening SpA among IBD patients.

We herein report a case involving a patient with quiescent ulcerative colitis (UC) in long-term clinical remission whose condition rapidly worsened after receiving a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, leading to colectomy due to toxic megacolon. The patient received the fifth dose of the Spikevax (mRNA-1273) vaccine and experienced a severe flare-up of UC 6 days later. Pathologic findings of the surgical specimens were consistent with severe active UC concomitant with cytomegalovirus infection. Because mRNA vaccines stimulate both humoral and cellular immunogenicity, it is important to note that they can be a triggering factor for the relapse of UC.