Analysis of the Dissolution Behavior of Theophylline and Its Cocrystal Using ATR-FTIR Spectroscopic Imaging.

Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic imaging is a powerful tool to visualize the distribution of components, and it has been used to analyze drug release from tablets. In this work, ATR-FTIR spectroscopic imaging was applied for observing the dissolution of molecular crystals from tablet compacts. The IR spectra provided chemically specific information about the transformation of crystal structures during the dissolution experiments. Theophylline (TPL) anhydrate and its cocrystals were used as model systems of molecular crystals. The IR spectra during the dissolution of TPL revealed information about the crystal structure of TPL, which transformed from anhydrate to monohydrate in water. During a dissolution test of a model cocrystal system, it was suggested that an active pharmaceutical ingredient (API) and a coformer were dissolved in water simultaneously. The IR spectra that were acquired during the dissolution of a cocrystal tablet showed new spectral bands attributed to the API after 5 min. This suggested that the precipitation of API was observed during the dissolution experiment. Measurements from ATR-FTIR spectroscopic imaging can visualize the drug release from the tablet and determine the transformation of molecular crystals during their dissolution. These results will have an impact on clarifying the dissolution mechanism of molecular crystals.

Prescribing in pregnant women with inflammatory bowel disease and its relationship to congenital malformations in Japan.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) frequently affects younger patients and poses various challenges concerning pregnancy and childbirth. Maintaining good disease control throughout pregnancy is crucial, but expectant and pregnant patients may worry about the fetal impact of medications, leading to treatment discontinuation due to uncertainty about this issue. This study investigated the real-world drug-prescribing practices for pregnant patients with IBD in Japan and their potential connection to major congenital malformations (MCMs). METHODS: Overall, 277 female IBD patients who gave birth between 2010 and 2019 were selected from the JMDC claims database. The prescribing patterns of IBD medications and MCMs in the patients' offspring were analyzed. RESULTS: Among pregnant IBD patients, 74.4% received at least one medication from 90 days before pregnancy to 90 days after delivery. Trends in medication prescriptions during pregnancy in 2010-2019 revealed consistent use of oral 5-ASA, variable use of topical medications, a decrease in systemic steroids, and an increase in biologics. The prevalence of MCMs in children born to IBD-affected mothers did not differ significantly between those who did and did not receive IBD medications (8.6% vs 6.8%). Although circulatory system MCMs were slightly more common in the IBD medication group (4.9% vs 1.4%), this difference was not significant. Logistic regression analysis did not reveal an association between MCM risk and first-trimester use of IBD medications, including corticosteroids and biologics. CONCLUSIONS: This study provides insights into medication patterns in pregnant IBD patients and suggests no increased risk of MCMs associated with first-trimester IBD medication use.

HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn's disease patients.

Recently, the HLA-DQA1*05 (rs2097432) genetic variation has been reported to be linked to early infliximab (IFX) treatment failure in the Caucasian Crohn's disease (CD) population, but that evidence is scarce in the Asian population. This study aimed to investigate the relationship between rs2097432 and the cumulative discontinuation-free time of IFX (IFX persistence) in 189 Japanese biologics-naive CD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The C allele of rs2097432 significantly increased the risk of early discontinuation of IFX [Hazard ratio (HR) = 2.23 and P-value = 0.026]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B which attenuates macrophage-mediated inflammation, reached genome-wide significance (HR = 6.04 and P-value = 7.93E-9). Pathway analysis suggested association of signaling by PDGF and FCGR activation signaling with IFX persistence (P-value = 8.56E-5 and 5.80E-4, respectively).

Systematically Designed Surface and Morphology of Magnetite Nanoparticles Using Monocarboxylic Acid with Various Chain Lengths under Hydrothermal Condition.

Hydrothermal synthesis of surface-modified magnetite nanoparticles (NPs) was performed in a batch reactor at 200 °C for 20 min while using monocarboxylic acid with various alkyl chain lengths (C6 to C18) as surface modifiers. The short-chain cases (C6 to C12) successfully gave the surface-modified NPs with uniform shape and magnetite structure, while the long-chain cases (C14 to C18) gave the NPs with nonuniform shape and two structures (magnetite and hematite). Additionally, the synthesized NPs were revealed to have single crystallinity, high stability, and ferromagnetic property, which were useful for hyperthermia therapy via various characterization techniques. These investigations would guide the selection guidelines for a surface modifier to control the structure, surface, and magnetic properties of surface-modified magnetite NPs with high crystallinity and stability, particularly for hyperthermia therapy applications.

Reduced antiviral seropositivity among patients with inflammatory bowel disease treated with immunosuppressive agents.

BACKGROUND: Although live-attenuated vaccines are contraindicated under immunosuppression, the immune status of patients with inflammatory bowel disease (IBD) has not been fully assessed prior to immunosuppressive therapy. AIMS: To investigate antiviral serostatus against viruses requiring live vaccines for prevention in IBD patients undergoing immunosuppressive therapy. METHODS: This multicenter study included IBD patients who were aged <40 years and were treated with thiopurine monotherapy, molecular-targeted monotherapy, or combination therapy. Gender- and age-matched healthy subjects (HS) living in the same areas were included as control group. Antibody titers against measles, rubella, mumps, and varicella were measured by enzyme-linked immunosorbent assays. RESULTS: A total of 437 IBD patients (163 ulcerative colitis [UC] and 274 Crohn's disease [CD]) and 225 HS were included in the final analysis. Compared with HS, IBD patients had lower seropositivity rates for measles (IBD vs. HS = 83.91% vs. 85.33%), rubella (77.55% vs. 84.89%), mumps (37.50% vs. 37.78%), and varicella (91.26% vs. 96.44%). Gender- and age-adjusted seropositivity rates were lower in UC patients than in both CD patients and HS for measles (UC, CD, and HS = 81.60%, 85.29%, and 85.33%), rubella (76.40%, 78.23%, and 84.89%), mumps (27.16%, 43.70%, and 37.78%), and varicella (90.80%, 91.54%, and 96.44%); the difference was significant for all viruses except measles. Divided by the degree of immunosuppression, there were no significant differences in seropositivity rates among IBD patients. CONCLUSIONS: IBD patients, especially those with UC, exhibit reduced seropositivity rates and may benefit from screening prior to the initiation of immunosuppressive therapy.

Usefulness and difficulties with the thiopurine pharmacogenomic NUDT15 genotyping test: Analysis of real-world data in Japan.

The usefulness of NUDT15 genotyping as a pharmacogenomic test for thiopurine has been established. The first such test developed to date, NUDT15 genotyping was approved for reimbursement in Japan in February 2019 for all indicated patients. We retrospectively examined claims data in Japan and confirmed that the proportion of patients who undergo genotyping before initiating a new thiopurine regimen has increased; furthermore, genotyping has improved the rate of treatment continuation and reduced on-treatment hospitalization. However, the genotyping rate before thiopurine induction was >50% for patients with inflammatory bowel disease and <20% for those with other immune-related diseases, indicating significant variation by disease field. Additionally, over 10% of tests were found to have been performed inappropriately, such as multiple genotyping of the same patient or testing more than 2 weeks after starting treatment. Although NUDT15 genotyping for patients requiring thiopurine treatment has been shown to improve thiopurine treatment continuation rate, measures are required to address the systematic issues identified in our analysis.

Response to COVID-19 vaccine is reduced in patients with inflammatory bowel disease, but improved with additional dose.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination is recommended for patients with inflammatory bowel disease (IBD); however, suppressed immune responses have been reported for fully vaccinated patients under immunosuppressive therapy, mainly from Western countries. We prospectively analyzed antibody titers of IBD patients in Asia induced by two-dose and additional dose of messengerRNA COVID-19 vaccine. METHODS: After measuring high-affinity antibody titers, factors associated with antibody titers were identified by multiple regression analyses using the following covariates: sex, age (≥60 or <60 years), disease type (Crohn's disease or ulcerative colitis), vaccine type (BNT162b2 or mRNA-1273), time from second/third vaccination, molecular-targeted agent (anti-tumor necrosis factor [TNF] agents, ustekinumab, vedolizumab, tofacitinib, or no molecular-targeted agents), thiopurine, steroid, and 5-aminosalicylic acid. RESULTS: Among 409 patients analyzed, mean titer was 1316.7 U/mL (SD, 1799.3); 403 (98.5%) were judged to be seropositive (≥0.8 U/mL), and 389 (95.1%) had neutralizing antibodies (≥15 U/mL). After the third vaccination, mean titer raised up to 21 123.8 U/mL (SD, 23 474.5); all 179 were seropositive, and 178 (99.4%) had neutralizing antibodies. In 248 patients with genetic data, there was no difference in mean titer after two/third doses between carriers and non-carriers of HLA-A24 associated with severe disease during COVID-19 infection. A multiple regression analyses using covariates revealed that older age, vaccine type (BNT162b2), time from second/third dose, anti-TNF agent, tofacitinib, and thiopurine were independently associated with lower antibody titers. CONCLUSIONS: Our findings further support the recommendation for COVID-19 vaccination in patients under immunosuppressive therapy, especially additional third dose for patients receiving anti-TNF agents and/or thiopurine or tofacitinib.

Serum leucine-rich alpha-2 glycoprotein as a predictive factor of endoscopic remission in Crohn's disease.

BACKGROUND AND AIM: The usefulness of fecal calprotectin (FC) and serum leucine-rich alpha-2 glycoprotein (LRG) assessing the activity of Crohn's disease (CD) remains to be fully demonstrated in Asia. The present study aimed to elucidate whether FC and LRG could predict endoscopic remission (ER) in Japanese patients with CD. METHODS: Between October 2018 and July 2021, we prospectively observed treatment courses of CD patients treated with biologic agents. The optimal cutoff values of Crohn's Disease Activity Index (CDAI), serum C-reactive protein (CRP), serum albumin (Alb), FC, and LRG levels for predicting ER at week 52 were calculated using receiver operating characteristic (ROC) curves. We also analyzed the correlations between the achievement of clinical remission (CR) or biomarker remission (BR) at week 12/24/52 and ER at week 52. RESULTS: Among 53 patients who completed 52 weeks of observation, 20 (37.7%) achieved ER at week 52. Using the calculated cutoff values, patients who achieved CR (CDAI ≤ 112) or BR (CRP ≤ 0.42 mg/dL, Alb ≥ 3.8 g/dL, FC ≤ 287 µg/g, or LRG ≤ 13.6 µg/mL) at week 12/24/52 had a higher ER rate at week 52. FC-BR at week 12/24 showed low sensitivity (0.58/0.60) but high specificity (0.78/0.74) for predicting ER; LRG-BR at week 12/24 also showed low sensitivity (0.68/0.74) but high specificity (0.87/0.78). However, FC-BR and LRG-BR at week 52 had improved sensitivity (0.80/0.84) while specificity remained (0.79/0.85). CONCLUSIONS: From the early phase of biologic treatment, both FC and LRG had high specificity for predicting ER at week 52. LRG showed higher sensitivity than FC.

Effectiveness of colonic stent placement for obstructive colorectal cancers: An analysis of short-term results using a nationwide database in Japan.

BACKGROUND AND AIMS: Self-expandable metallic stent (SEMS) is widely used for obstructive colorectal cancer (OCC). Both SEMS and urgent surgery have several merits and demerits. This study aimed to clarify the efficacy of SEMS by comparing the mortality rate after the hospitalization between SEMS and urgent surgery for OCC. METHODS: We collected OCC patients' data using the Diagnosis Procedure Combination (DPC) database system. We divided eligible patients into the SEMS and urgent surgery groups using propensity score matching and compared in-hospital death rates, length of hospitalization, and medical costs. We also conducted logistic regression analysis to identify clinical factors affecting in-hospital deaths. RESULTS: We enrolled 17 140 cases after propensity score matching. SEMS reduced the in-hospital death rate compared with urgent surgery (2.0% vs 3.6%, P < 0.0001). Length of hospitalization was shorter in the SEMS group than in the urgent surgery group (16 vs 25 days, P < 0.0001). Medical costs were lower in the SEMS group than in the urgent surgery group (1 663 550 vs 2 424 082 JPY, P < 0.0001). Multivariate analysis also showed that SEMS reduced in-hospital death (odds ratio = 0.58, 95% confidence interval: 0.50-0.70, P < 0.0001). CONCLUSION: Self-expandable metallic stent placement for OCC might reduce the mortality rate in short term and shorten the length of hospitalization. These results facilitate considering SEMS with careful judgment for its indication when treating OCC patients.

Endoscopic radial incision and cutting for benign stenosis of the lower gastrointestinal tract: An investigation of novel endoscopic treatment in multicenter trial.

BACKGROUND AND AIM: The standard therapies for benign gastrointestinal stenosis are endoscopic balloon dilation or surgery; each have their advantages and disadvantages. In contrast, radial incision and cutting (RIC) is a novel approach for such stenosis. This study aimed to investigate the feasibility, safety, and effectiveness of RIC. METHODS: We enrolled 20 patients with benign stenosis of the lower gastrointestinal tract developed by various causes and conducted RIC. We evaluated the re-intervention free rate 52 weeks after RIC, technical success rate, adverse events, procedure time, and improvement of symptoms using a visual analog scale. RESULTS: We performed 20 sessions of first RIC for 20 lesions and seven sessions of additional RIC due to re-stenosis. The cumulative re-intervention-free survival rate 52 weeks after the first RIC was 55.8%. The technical success rate of the first RIC was 100% (20/20) while that of the additional RIC was 85.7% (6/7). One case developed perforation during the additional RIC and urgent surgery was performed. The additional RIC tended to show worse results in adverse events and procedure time compared with the first RIC. The patients' symptoms including abdominal bloating and dyschezia were significantly improved. CONCLUSIONS: Although RIC demonstrated a higher technical success rate for lower gastrointestinal stricture and subsequent improvement of patient symptoms, several issues including preventing delayed bleeding, perforation, and the long-term prognosis should be solved and clarified in further investigations.

Long-term effectiveness of ustekinumab comparable to antitumor necrosis factor agents in patients with Crohn's disease.

BACKGROUND: Ustekinumab (UST), an antibody against the p40 subunit of interleukin-12/23, has been proven to be effective in patients with Crohn's disease (CD). However, large, long-term comparative studies of UST against anti--tumor necrosis factor (TNF) agents are lacking. We compared the effectiveness of anti-TNF agents and UST in CD patients without prior use of biologics. METHODS: We used a large nationwide anonymized Japanese database containing administrative medical claims data and various related patient data. In a propensity score-matched cohort with similar clinical characteristics, 2-year effectiveness was compared between patients treated with infliximab or adalimumab (anti-TNF group) and those treated with UST (UST group). Primary outcomes were cumulative rates of hospitalization, surgery, and persistence. RESULTS: Among 53 540 CD patients, 7047 were extracted for eligibility, of which 5665 were treated with an anti-TNF agent and 1382 with UST. After propensity score matching, the cumulative hospitalization rates were comparable between anti-TNF and UST groups (P = 0.85; 25.3% vs 26.5% at 1 year, 33.8% vs 39.8% at 2 years). The cumulative surgery rates were also comparable between these groups (P = 0.46; 5.5% vs 5.1% at 1 year, 8.3% vs 8.4% at 2 years). The persistence rate at 1 year was higher in UST group (90.8% vs 92.5%), and that at 2 years was higher in anti-TNF group (81.2% and 74.6%); however, there was no significant difference in the cumulative persistence rate (P = 0.55). CONCLUSIONS: Anti-TNF agents and UST appear to have comparable effectiveness for CD patients without prior use of biologics.

Capsule Endoscopy Is Useful for Postoperative Tight Control Management in Patients with Crohn's Disease.

BACKGROUND: In Crohn's disease, postoperative endoscopic activity of small bowel lesions outside the scope of ileocolonoscopy has been insufficiently studied. AIMS: We aimed to assess this postoperative activity using capsule endoscopy (CE) and analyze the association between treatment optimization based on CE findings and the long-term course. METHODS: In patients who underwent intestinal resection, we performed CE and assessed the endoscopic activity using the Lewis score within 3 months postoperatively (1st CE) and during follow-up. Postoperative treatments were adjusted according to clinical symptoms or CE findings (severity of 1st CE or worsening of follow-up CEs). Hospitalization, repeat surgery, or endoscopic dilation defined the primary outcome. RESULTS: Among the CE group (N = 48), 85.7% (1st CE) and 79.2% (2nd CE) exhibited endoscopic activities indicating residual or recurrent lesions. Postoperative treatments were adjusted according to clinical symptoms in the non-CE group (N = 57) and clinical symptoms or CE findings in the CE group. Compared to the non-CE group, the CE group had significantly fewer primary outcomes. Patients with treatment adjustments based on CE findings had even lower primary outcome rate. Multivariate analysis identified the CE group as an independent protective factor (hazard ratio = 0.45, 95% confidence interval = 0.20-0.96). Treatment adjustments based on CE findings showed a stronger protective effect (0.30, 0.10-0.75). CONCLUSIONS: Postoperative repeated CE enabled us to assess residual and recurrent lesions accurately before clinical symptoms appeared. The regular assessment of endoscopic activity and subsequent treatment optimization have the potential for improving postoperative course.

Efficacy of urgent colonoscopy for colonic diverticular bleeding: A propensity score-matched analysis using a nationwide database in Japan.

BACKGROUND AND AIM: Although colonic diverticular bleeding (CDB) is considered to have good prognosis with conservative therapy, some cases are severe. The efficacy of urgent colonoscopy for CDB and clinical factors affecting CDB prognosis are unclear. This study aimed to evaluate the efficacy of urgent colonoscopy for CDB and identify risk factors for unfavorable events, including in-hospital death during admission, owing to CDB. METHODS: We collected CDB patients' data using the Diagnosis Procedure Combination database system. We divided eligible patients into urgent and elective colonoscopy groups using propensity score matching and compared endoscopic hemostasis and in-hospital death rates and length of hospital stay. We also conducted logistic regression analysis to identify clinical factors affecting CBD clinical events, including in-hospital death, a relatively rare CDB complication. RESULTS: Urgent colonoscopy reduced the in-hospital death rate (0.35% vs 0.58%, P = 0.033) and increased the endoscopic hemostasis rate (3.0% vs 1.7%, P < 0.0001) compared with elective colonoscopy. Length of hospitalization was shorter in the urgent than in the elective colonoscopy group (8 vs 9 days, P < 0.0001). Multivariate analysis also revealed that urgent colonoscopy reduced in-hospital death (odds ratio = 0.67, 95% confidence interval: 0.46-0.97, P = 0.036) and increased endoscopic hemostasis (odds ratio = 1.84, 95% confidence interval: 1.53-2.22, P <  0.0001). CONCLUSION: Urgent colonoscopy for CDB may facilitate identification of the bleeding site and reduce in-hospital death. The necessity and appropriate timing of urgent colonoscopy should be considered based on patients' condition.

Field-induced superconducting phase of FeSe in the BCS-BEC cross-over.

Fermi systems in the cross-over regime between weakly coupled Bardeen-Cooper-Schrieffer (BCS) and strongly coupled Bose-Einstein-condensate (BEC) limits are among the most fascinating objects to study the behavior of an assembly of strongly interacting particles. The physics of this cross-over has been of considerable interest both in the fields of condensed matter and ultracold atoms. One of the most challenging issues in this regime is the effect of large spin imbalance on a Fermi system under magnetic fields. Although several exotic physical properties have been predicted theoretically, the experimental realization of such an unusual superconducting state has not been achieved so far. Here we show that pure single crystals of superconducting FeSe offer the possibility to enter the previously unexplored realm where the three energies, Fermi energy εF, superconducting gap Δ, and Zeeman energy, become comparable. Through the superfluid response, transport, thermoelectric response, and spectroscopic-imaging scanning tunneling microscopy, we demonstrate that εF of FeSe is extremely small, with the ratio Δ/εF ~ 1(~0.3) in the electron (hole) band. Moreover, thermal-conductivity measurements give evidence of a distinct phase line below the upper critical field, where the Zeeman energy becomes comparable to εF and Δ. The observation of this field-induced phase provides insights into previously poorly understood aspects of the highly spin-polarized Fermi liquid in the BCS-BEC cross-over regime.

Usefulness of a peripherally inserted central catheter for total parenteral nutrition in patients with inflammatory bowel disease.

BACKGROUNDS AND AIMS: Peripherally inserted central catheters (PICC) have been widely used as a blood access route for total parenteral nutrition (TPN) in recent years. However, there have been few reports that evaluated the usefulness of PICC for patients with inflammatory bowel disease (IBD). In this study, we compared the clinical courses in patients with IBD who received TPN during their hospitalization by conventional central venous catheters (CVC) and PICC. PATIENTS AND METHODS: A total of 137 IBD patients were enrolled. The CVC group and the PICC group included 56 and 81 patients, respectively. The clinical courses in both groups were compared retrospectively. RESULTS: As a complication of the puncture, pneumothorax occurred in two patients (3.6%) in the CVC group, but in none (0%) in the PICC group. The PICC group had significantly higher rates of achieving the scheduled TPN without removing the catheter, lower rates of catheter-related blood stream infection (CRBSI) and longer periods without CRBSI than the CVC group. CONCLUSION: PICC might be more useful than CVC in terms of safety and the ability to deliver scheduled TPN for IBD patients.

Low temperature synthesis of ZnO particles using a CO2-driven mechanism under high pressure.

Low temperature synthesis of ZnO particles without using reactive materials, solvents and post-treatments is still a serious challenge for both fundamental research and industrial applications. In this research, we report the dry synthesis of ZnO particles only by using Zn(acac)2 and supercritical CO2 (scCO2) at the low temperature of 60 °C. The synthesis was performed using CO2 and N2 from 0.1 to 30.0 MPa for 18 h. As a result, ZnO yields increased with a rise in the CO2 pressure and reached 67% at 30.0 MPa while N2 medium gave low yields below 4.9% regardless of the pressure. Additionally, the detailed characterization results and the phase behavior observations evidentially showed the formation of zinc-CO/CO2-organic complexes in the solid phase of Zn(acac)2 powder under scCO2, resulting in the accelerated formation of ZnO particles. These findings suggest that scCO2 has potential value to drive the formation reaction of zinc-CO/CO2-organic complexes, which allows the low temperature synthesis of ZnO particles under dry conditions without using reactive materials, solvents and post-treatments.

Clinical practice and outcome of patients with elderly-onset ulcerative colitis: Insights from a nationwide claims database study in Japan.

Background and Aim: The number of older patients with ulcerative colitis is increasing; however, limited data exist regarding the differences between elderly- and non-elderly-onset ulcerative colitis. We aimed to compare the clinical practice and course of elderly-onset ulcerative colitis with those of non-elderly-onset ulcerative colitis. Methods: We selected older patients with ulcerative colitis and divided them into the elderly- and non-elderly-onset ulcerative colitis groups according to their age at onset. We compared the cumulative systemic steroid-free, molecular targeting drug-free, and surgery-free rates between the two groups. We performed a multivariate analysis to identify the clinical factors related to systemic steroid administration, the use of molecular targeting drugs, surgery, and death. Results: We collected data of 2669 and 277 elderly and non-elderly-onset ulcerative colitis patients, respectively. The cumulative systemic steroid-free rate of elderly-onset ulcerative colitis was significantly lower than that of non-elderly-onset ulcerative colitis. However, no difference was observed in the cumulative molecular targeting drugs and surgery-free rates between the two groups. Elderly-onset ulcerative colitis significantly increased the risk of systemic steroid administration and death but not the use of molecular targeting drugs and surgery. Conclusion: The disease severity of ulcerative colitis and clinical practice may not differ between the elderly- and non-elderly-onset groups. However, elderly-onset ulcerative colitis was associated with increased mortality risk. Thus, we need to pay attention to the patients' condition and appropriate timing of surgery for patients with elderly-onset ulcerative colitis.

Live-attenuated vaccination in patients with inflammatory bowel disease while continuing or after elective switch to vedolizumab.

Background/Aims: Vedolizumab (VDZ) is a gut-selective agent with a favorable safety profile. We aimed to assess the feasibility of elective switch from other advanced therapies to VDZ and subsequent live-attenuated vaccination while continuing VDZ in patients with inflammatory bowel diseases (IBD). Methods: We measured antibody titers specific for measles, rubella, mumps, and varicella viruses in IBD patients under immunosuppressive therapy. Those with negative titers and without vaccination history were judged unimmunized. Patients were administered vaccines while continuing VDZ or switched to VDZ if receiving other advanced therapies and then administered vaccines. Co-primary outcomes were the rate of maintaining disease severity after vaccination and the rate without vaccine-induced infection. Results: Among 107 unimmunized patients, 37 agreed to receive live-attenuated vaccines while continuing VDZ (17 patients) or after switching to VDZ (20 patients). In the 20 patients who electively switched to VDZ, disease severity was maintained except for 1 patient who developed intestinal infection. After 54 weeks, 18 patients (90%) continued to receive VDZ, excluding 2 patients who reverted to their originally administered biologics. In all 37 patients administered live-attenuated vaccines under VDZ treatment, disease severity was maintained after vaccination. Antibody titers became positive or equivocal in 34 patients (91.9%). There were no cases of vaccine-induced infection during a median observation period of 121 weeks. Conclusions: While live-attenuated vaccines are contraindicated under immunosuppressive therapy, they may be safely administered while receiving VDZ immunotherapy. Switching from other advanced therapies to VDZ and subsequently receiving live-attenuated vaccines may be a safe alternative in unimmunized patients.

Clinical Utilization of Generic Drugs and Biosimilars for Ulcerative Colitis Treatment: Insights from a Nationwide Database Study in Japan.

Introduction: Limited data exist regarding the prevalence and clinical practice involving generic drugs and biosimilars for treating ulcerative colitis (UC) in Japan. We aimed to clarify the clinical usage of these generic drugs and biosimilars for UC treatment in Japan using a nationwide database. Methods: We collected data from 30,675 UC cases, along with their prescriptions for both generic drugs or biosimilars and their original counterparts, using a medical claim database provided by DeSC Healthcare, Inc. We calculated the prescription and penetration rates of generic drugs and biosimilars and demonstrated the transition of these rates. Additionally, the cumulative retention rates between infliximab originator and biosimilar were compared using the Kaplan-Meier method. Results: The prescription rate of generic mesalazine increased from approximately 10% in 2015 to over 30% in 2021. Although the prescription rate of generic molecular targeting drugs (MTDs) also increased from approximately 0.15% in 2014 to 2.5% in 2021, the increment was lower than that of generic mesalazine. The penetration rates of generic 5-aminosalicylic acid and tacrolimus ranged from over 30% to approximately 50%. Infliximab biosimilar achieved an approximate 20% penetration rate, whereas adalimumab achieved <5%. The cumulative retention rates did not differ between infliximab originator and biosimilar. Conclusions: The penetration rates of generics and biosimilars for UC treatment are relatively low compared with those for treatment in other fields and the goal of the Ministry of Health, Labor, and Welfare. Several countermeasures are necessary for the widespread use of generics and biosimilars, ultimately contributing to cost-effective and sustainable healthcare delivery.