Clinical Remission Rates Research Articles

Tofacitinib for the treatment of immune-related adverse events in cancer immunotherapy: a multi-center observational study

BackgroundTreatment strategy against immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) frequently requires other immunosuppressive agents. Tofacitinib is a rapidly acting JAK-STAT inhibitor with proven efficacy in multiple autoimmune diseases. We aimed to evaluate the efficacy and safety of tofacitinib in the management of irAEs in cancer patients.MethodsCancer patients who received ICIs and were treated with tofacitinib for the management of irAEs at 6 institutions were retrospectively included in this study. Demographic and clinical characteristics were obtained from electronic medical records. Longitudinal assessment of cardiac troponin T (cTnT) with clinical assessment was utilized to evaluate the benefit of tofacitinib treatment in patients with ICI myocarditis. Overall survival (OS) was also assessed.ResultsFifty-three patients were included in this study. The median time from irAE onset to tofacitinib therapy was 17 (range, 2–186) days and the median duration of tofacitinib treatment was 52.5 (range, 3–277) days. Enrolled patients were subdivided into 3 groups based on clinical severity and steroid responsiveness including 11 life-threatening cases, 30 steroid-resistant cases, and 12 cases with steroid taper failure. Clinical remission rate in each group was 54.5%, 96.7%, and 100%, respectively (P < 0.01). Tofacitinib was well-tolerated with 4 patients (7.5%) developing infectious events. From the ICI initiation, the overall median OS was 16.1 (95% CI 7.8–26.9) months.ConclusionTofacitinib showed promising clinical efficacy in patients experiencing irAEs, particularly in patients who failed to respond to steroids or experienced relapse during steroid tapering. Moreover, and most importantly, tofacitinib exhibited a favorable safety profile in cancer patients developing irAEs in terms of both toxicity and anti-tumor activity. Future prospective studies are warranted.

Enhancing Oral 5-ASA Effectiveness in Mild-to-Moderate Ulcerative Colitis through an H. erinaceus-Based Nutraceutical Add-on Multi-Compound: The "HERICIUM-UC" Two-Arm Multicentre Retrospective Study.

Mild-to-moderate ulcerative colitis (UC) management is centred on 5-aminosalicylic acid (5-ASA) derivatives. Whether supplementing 5-ASA with nutraceuticals can provide real advantages in UC-relevant outcomes is unclear. This retrospective multicentre study compared clinical remission, response rates, and faecal calprotectin levels in a two-arm design, including patients treated with 5-ASA alone and those with additional H. erinaceus-based multi-compound supplementation. In the 5-ASA alone group, clinical response rates were 41% at three months (T1) and 60.2% at six months (T2), while corresponding clinical remission rates were 16.9% and 36.1%. In the nutraceutical supplementation group, clinical response rates were 49.6% (T1) and 70.4% (T2), with clinical remission rates of 30.4% (T1) and 50.9% (T2). No significant differences in clinical response rates between the groups at T1 (p = 0.231) and T2 (p = 0.143) emerged. Clinical remission rates differed significantly at both time points (p = 0.029 and p = 0.042, respectively). Faecal calprotectin levels decreased significantly in both groups during the retrospective follow-up (p < 0.05), and this was more pronounced in nutraceutical supplementation patients at both T1 (p = 0.005) and T2 (p = 0.01). No adverse events were reported. This multi-component nutraceutical supplementation offers real-world potential in controlling disease activity in patients with mild-to-moderate UC.

Optimising infliximab induction dosing to achieve clinical remission in Chinese patients with Crohn's disease.

A strategy based on therapeutic drug monitoring and population pharmacokinetic (popPK) models would likely increase the rate of clinical remission (CR) after infliximab (IFX) induction in patients with Crohn's disease (CD). This study aimed to evaluate the relationship between early IFX levels and antibodies to infliximab (ATI) and CR at week 14 and simulate the probability of attaining the identified exposure target. Patients with CD (n = 140) treated with IFX were enrolled to develop the popPK model. Of these, 43 moderate-to-severe patients with CD were followed up at week 14. Simulations were performed on patients with different dosage regimens and covariates. IFX levels >20.08μg/mL at week 2, >18.44μg/mL at week 6, and >3.08μg/mL at week 14 were linked to CR. A one-compartment model fit the data best. The covariates influencing clearance were fat free mass, albumin and ATI levels. To achieve IFX levels >20.08μg/mL at week 2, ≥400mg IFX was predicted to be required in over 50% patients with 45-70kg and 35-45g/L albumin, except for patients with 70kg and 30g/L albumin. IFX levels >20.08μg/mL at week 2 and absence of ATI at week 14 are associated with CR. Optimising IFX induction dosing will be critical to achieve the target of early IFX levels associated with CR.

Decitabine-based treatment strategy improved the outcome of HSCT in JMML: a retrospective cohort study.

Pre-HSCT disease control, suboptimal long-term prognosis, and a high recurrence incidence (RI) continue to pose significant challenges for hematopoietic stem cell transplantation (HSCT) in juvenile myelomonocytic leukemia (JMML) patients. This retrospective cohort study assessed the effectiveness of a decitabine (DAC)-based protocol in JMML patients undergoing HSCT. The pre-HSCT treatment includes initial and bridging treatment. The efficacy of DAC monotherapy versus DAC combined with cytotoxic chemotherapy(C-DAC) as initial treatment was compared, followed by DAC plus FLAG (fludarabine, cytarabine, and GCSF) as bridging treatment. The HSCT regimens were based on DAC, fludarabine, and busulfan. Post-HSCT, low-dose DAC was used as maintenance therapy. The study endpoints focused on pretransplantation simplified clinical response and post-HSCT survival. There were 109 patients, including 45 receiving DAC monotherapy and 64 undergoing C-DAC treatment. 106 patients completed bridging treatment. All patients were administered planned HSCT regimens and post-HSCT treatment. The initial treatment resulted in 88.1% of patients achieving clinical remission without a significant difference between the DAC and C-DAC groups (p=0.769). Clinical remission rates significantly improved following bridging treatment (p=0.019). The 5-year overall survival, leukemia-free survival, and RI were 92.2%, 88.4%, and 8.0%, respectively. A poor clinical response to pre-HSCT treatment emerged as a risk factor for OS (hazard ratio: 9.8, 95% CI: 2.3-41.1, p=0.002). Implementing a DAC-based administration strategy throughout the pre-HSCT period, during HSCT regimens, and in post-HSCT maintenance significantly reduced relapse and improved survival in JMML patients. Both DAC monotherapy and the DAC plus FLAG protocol proved effective as pre-HSCT treatments.

Home-based transcranial direct current stimulation in bipolar depression: an open-label treatment study of clinical outcomes, acceptability and adverse events

BackgroundCurrent treatments for bipolar depression have limited effectiveness, tolerability and acceptability. Transcranial direct current stimulation (tDCS) is a novel non-invasive brain stimulation method that has demonstrated treatment efficacy for major depressive episodes. tDCS is portable, safe, and individuals like having sessions at home. We developed a home-based protocol with real-time remote supervision. In the present study, we have examined the clinical outcomes, acceptability and feasibility of home-based tDCS treatment in bipolar depression.ResultsParticipants were 44 individuals with bipolar disorder (31 women), mean age 47.27 ± 12.89 years, in current depressive episode of at least moderate severity (mean Montgomery Asberg Depression Rating Scale (MADRS) score 24.59 ± 2.64). tDCS was provided in bilateral frontal montage, F3 anode, F4 cathode, 2 mA, for 30 min, in a 6-week trial, for total 21 sessions, a follow up visit was conducted 5 months from baseline. Participants maintained their current treatment (psychotherapy, antidepressant or mood stabilising medication) or maintained being medication-free. A research team member was present by video conference at each session. 93.2% participants (n = 41) completed the 6-week treatment and 72.7% of participants (n = 32) completed the 5 month follow up. There was a significant improvement in depressive symptoms following treatment (mean MADRS 8.77 ± 5.37) which was maintained at the 5 month follow up (mean MADRS 10.86 ± 6.90), rate of clinical response was 77.3% (MADRS improvement of 50% or greater from baseline), and rate of clinical remission was 47.7% (MADRS rating of 9 or less). Acceptability was endorsed as “very acceptable” or “quite acceptable” by all participants. No participants developed mania or hypomania.ConclusionsIn summary, home-based tDCS with real-time supervision was associated with significant clinical improvements and high acceptability in bipolar depression. Due to the open-label design, efficacy findings are preliminary.Trial registrationClinicalTrials.gov number NCT05436613 registered on 23 June 2022 https//www.clinicaltrials.gov/study/NCT05436613.

Safety and effectiveness of tofacitinib in Korean adult patients with ulcerative colitis: post-marketing surveillance study

BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We aimed to identify the safety and effectiveness of tofacitinib in patients with UC in routine clinical settings in Korea.MethodsThis open-label, observational, prospective, post-marketing surveillance study was conducted at 22 hospitals in the Republic of Korea. Patients with moderate to severe active UC who received tofacitinib were included and followed up for up to 52 weeks. Tofacitinib was administered at a dosage of 10 mg twice daily for at least 8 weeks, followed by 5 or 10 mg twice daily at the investigator’s discretion based on clinical evaluation according to the approved Korean label. Safety including adverse events (AEs) and effectiveness including clinical remission, clinical response, and endoscopic mucosal healing were evaluated. Safety analysis set was defined as all patients registered for this study who received at least one dose of tofacitinib according to the approved Korean label and followed up for safety data. Effectiveness analysis set included patients in the safety analysis set who were evaluated for overall effectiveness assessment and excluded patients who had received tofacitinib less than 8 weeks.ResultsA total of 110 patients were enrolled, of whom 106 patients were included in the safety population. The median duration of treatment was 370 days and the treatment duration ranged from 16 to 684 days for the safety population. AEs occurred in 42 patients (39.6%). Serious AEs (SAEs) occurred in 7 patients (6.6%) and of them, there were 2 cases of serious infections. These serious infections were reported as Adverse Event of Special Interest (AESI) in this study and no other AESI were reported. There were no cases of death during the study period. Clinical remission rates were 40.0%, 46.7%, 57.6%, and 55.1% at 8, 16, 24, and 52 weeks, and clinical response rates were 77.8%, 87.9%, 56.6%, and 81.4% at each visit, respectively. Endoscopic mucosal healing rates were 58.7% at 16 weeks and 46.2% at 52 weeks.ConclusionTofacitinib was effective in Korean patients with moderate to severe active UC and the safety findings were consistent with the known safety profile of tofacitinib.SummaryThis study confirmed the safety and effectiveness of tofacitinib in Korean patients with moderate to severe active UC in routine clinical settings.Trial registrationThis study is registered in the ClinicalTrials.gov under the identifier NCT04071405, registered on 28 August 2019.

Comparative Safety and Effectiveness of Ustekinumab and Anti-TNF in Elderly Crohn's Disease Patients.

Biologic therapies are associated with increased infection risk among elderly patients with inflammatory bowel disease (IBD). However, there are few data on the safety and effectiveness of ustekinumab compared with anti-tumor necrosis factor (anti-TNF) agents in the elderly. The study sought to compare the safety and effectiveness of ustekinumab and anti-TNF agents in elderly Crohn's disease (CD) patients. Patients ≥60 years of age who commenced ustekinumab or an anti-TNF agent for CD were included in this retrospective multicenter cohort. The primary outcome was incidence of serious infections requiring hospitalization. Effectiveness was assessed by clinical remission, clinical response, and treatment persistence rates at 6 months. We adjusted for confounders using inverse probability of treatment weighting (IPTW) and performed a logistic regression analysis to assess factors associated with serious infections, clinical remission, and treatment persistence. Eighty-three patients commencing ustekinumab and 124 commencing anti-TNF therapy were included. There was no difference in serious infection rates between anti-TNF agents (2.8%) and ustekinumab (3.1%) (P = .924) after propensity adjustment. Clinical remission rates were comparable at 6 months for ustekinumab (55.9%) and anti-TNF agents (52.4%) (P = .762). There was a significant reduction in HBI at 6 months in both groups. Treatment persistence was comparable between ustekinumab (90.6%) and anti-TNF agents (90.0%) at 6 months. Cox regression analysis did not show differences in treatment persistence (hazard ratio, 1.23; 95% confidence interval, 0.57-2.61; P = .594) and serious infection incidence (hazard ratio, 1.38; 95% confidence interval, 0.25-7.57; P = .709) by 6 months. We observed comparable safety and effectiveness for ustekinumab and anti-TNF agents in treating elderly CD patients.

One-year Safety and Effectiveness of Ustekinumab in Patients With Crohn's Disease: The K-STAR Study.

This study investigated the safety and effectiveness of ustekinumab (UST) in Korean patients with Crohn's disease (CD). Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn's Disease patients treated with STelARa) study between April 2018 and April 2022. Both the clinical effectiveness and adverse effects of UST therapy were analyzed. Missing data were handled using nonresponder imputation (ClinicalTrials.gov Identifier: NCT03942120). Of the 464 patients enrolled from 44 hospitals across Korea, 457 and 428 patients (Crohn's disease activity index ≥150) were included in the safety analysis and effectiveness analysis sets, respectively. At weeks 16 to 20 after initiating UST, clinical response, clinical remission, and corticosteroid-free remission rates were 75.0% (321 of 428), 64.0% (274 of 428), and 61.9% (265 of 428), respectively. At week 52 to 66, clinical response, clinical remission, and corticosteroid-free remission rates were 62.4% (267 of 428), 52.6% (225 of 428), and 50.0% (214 of 428), respectively. Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171 of 428) and 41.6% (178 of 428) at week 16 to 20 and week 52 to 66, respectively. Biologic-naïve patients exhibited significantly higher rates of combined effectiveness than biologic-experienced patients (50.3% vs 30.7% at week 16-20, P < .001; 47.7% vs 36.0% at week 52-66, P = .014). No additional benefits were observed with the concomitant use of immunomodulators. Ileal location was independently associated with a higher probability of clinical remission compared with colonic or ileocolonic location at week 52 to 66. Adverse and serious adverse events were observed in 28.2% (129 of 457) and 12.7% (58 of 457), respectively, with no new safety signal associated with UST treatment. Ustekinumab was well-tolerated, effective, and safe as induction and maintenance therapy for CD in Korea.

Real-world Clinical Effectiveness and Safety of Vedolizumab and Adalimumab in Biologic-naive Patients With Crohn's Disease: Results From the EVOLVE Study.

This study evaluated the real-world effectiveness and safety of vedolizumab versus adalimumab over 12 months of treatment in biologic-naive patients with Crohn's disease (CD), using data from the EVOLVE study. A comparison of vedolizumab and adalimumab may help to better position them in the therapeutic algorithm for moderate-to-severe CD. Data were collected from medical records of patients with CD aged ≥18 years initiating treatment with adalimumab or vedolizumab between May 2014 and July 2017. Adjusted analyses were performed using inverse probability weighting to account for differences in baseline characteristics. Cumulative rates for clinical effectiveness outcomes and treatment persistence were estimated using Kaplan-Meier analyses. Disease-related exacerbations, serious adverse events (SAEs), and serious infections (SIs) were also assessed. Data from 218 vedolizumab- and 144 adalimumab-treated patients were analyzed. Adjusted cumulative rates of clinical remission were greater with vedolizumab than with adalimumab (66.3% vs. 46.4%; P=0.006). Probability of treatment persistence was higher with vedolizumab (89.3% vs. 77.5%; P=0.024); probabilities of clinical response (68.5% vs. 61.1%; P=0.586) and mucosal healing (67.7% vs. 56.0%; P=0.562) were similar. SAEs were less likely to occur with vedolizumab [hazard ratio, 0.45 (95% confidence interval, 0.22-0.93)]; however, the likelihood of SIs [0.27 (0.06-1.20)], CD exacerbations [0.91 (0.56-1.47)], and CD-related surgeries [1.55 (0.21-11.15)] was comparable between the 2 groups. In a real-world setting, biologic-naive patients with CD treated with vedolizumab demonstrated a greater likelihood of drug persistence and achieving clinical remission, with equivalent rates of response and mucosal healing versus adalimumab-treated patients.

Mirikizumab: A promising breakthrough in Crohn's disease treatment.

Crohn's disease (CD) is a chronic, progressive inflammatory bowel disorder characterized by persistent inflammation and noncontiguous "skip lesions" throughout the gastrointestinal tract. With a prevalence of 100-300 cases per 100,000 individuals, CD is most common in Western Europe and North America. Symptoms include abdominal pain, diarrhea, fever, weight loss, and anemia, with severe cases leading to complications such as perianal abscesses and cutaneous fistulas. Treatment involves pharmaceutical interventions, bowel rest, and sometimes surgery, with biological therapies like ustekinumab and mirikizumab gaining prominence. The VIVID-1 trial assessed mirikizumab in patients with moderately to severely active CD. By Week 12, mirikizumab significantly outperformed placebo in clinical response (45.4% vs. 19.6%, p < 0.000001). By Week 52, it showed higher clinical remission rates (54.1% vs. 19.6%) and demonstrated non-inferiority to ustekinumab in clinical remission (p = 0.51). The SEQUENCE study compared risankizumab to ustekinumab, with risankizumab showing superior reductions in inflammatory markers and higher biologic remission rates at Weeks 8, 24, and 48. Both treatments had similar safety profiles, with common adverse events including COVID-19, anemia, and headache. Mirikizumab, based on the VIVID-1 trial outcomes, is a promising addition to CD therapy. It demonstrated significant clinical responses and remission rates, warranting further research on its long-term efficacy and safety. Updating professional guidelines and addressing affordability will ensure broader access and improved management of CD.

Long-Term Clinical and Sustained REMIssion in Severe Eosinophilic Asthma Treated With Mepolizumab: The REMI-M Study

Biological therapies, such as mepolizumab, have transformed the treatment of severe eosinophilic asthma. While mepolizumab's short-term effectiveness is established, there is limited evidence on its ability to achieve long-term clinical remission. To evaluate the long-term effectiveness and safety of mepolizumab, explore its potential to induce clinical and sustained remission, and identify baseline factors associated with the likelihood of achieving remission over 24 months. The REMI-M is a retrospective, real-world, multicenter study that analyzed 303 severe eosinophilic asthma patients who received mepolizumab. Clinical, demographic, and safety data were collected at baseline, 3, 6, 12, and 24 months. The most commonly used definitions of clinical remission, which included no exacerbations, no oral corticosteroids (OCS) use, and good asthma control with or without assessment of lung function parameters, were assessed. Sustained remission was defined as reaching clinical remission at 12 months and maintaining it until the end of the 24-month period. Clinical remission rates ranged from 28.6% to 43.2% after 12 months and from 26.8% to 52.9% after 24 months, based on the different remission definitions. The proportion of patients achieving sustained remission varied between 14.6% to 29%. Factors associated with the likelihood of achieving clinical remission included the presence of aspirin-exacerbated respiratory disease, better lung function at baseline, male sex, absence of anxiety/depression, gastro-esophageal reflux disease, bronchiectasis, and reduced OCS consumption. Adverse events were infrequent. This study demonstrates the real-world effectiveness of mepolizumab in achieving clinical remission and sustained remission in severe eosinophilic asthma over 24 months. The identification of distinct factors associated with the likelihood of achieving clinical remission emphasizes the importance of comprehensive management of comorbidities and timely identification of patients who may benefit from biologics.

Etiology, Clinical Characteristics and Prognosis of Secondary Hemophagocytic Syndrome

To understand the etiology, clinical characteristics and prognosis of secondary hemophagocytic syndrome (HLH), so as to improve the understanding of HLH and reduce the rates of misdiagnosis and missed diagnosis of HLH. A retrospective study was conducted to analyze the cause, clinical characteristics, laboratory findings, therapy and outcomes of 75 adult patients with secondary HLH admitted to our hospital from January 2015 to December 2021. Follow-up continued until the last discharge time. Among 75 patients, infection-related HLH was the most common (45.33%), followed by lymphoma-related HLH (17.33%). Fever was the most common clinical manifestation (97.67%). Laboratory indicators such as NK cell activity (98.31% low or absent), sCD25 (93.22% increased), and serum ferritin (94.44% elevated) had higher sensitivity in diagnosis. By comparing the clinical manifestations and laboratory indicators of HLH patients with different causes, sex, lymph node enlargement and bone marrow morphology were more valuable for the diagnosis of primary disease (all P <0.05). By comparing the treatment and clinical outcomes of HLH patients with different causes, the highest clinical remission rate (83.3%) was achieved in patients with autoimmune disease-related HLH treated with hormone+cyclosporine (P <0.05). The overall 12-month survival rate of all patients was 26.7%, in which the infection-related HLH was the lowest (14.7%) while autoimmune disease-related HLH was the highest (63.6%). The causes and clinical characteristics of adult secondary HLH are varied, with poor prognosis and heterogeneity in disease severity. It is important to identify HLH cause early for diagnosis and needed to further understand HLH.

Mucosal and Transmural Healing and Long-term Outcomes in Crohn's Disease.

Healing in Crohn's disease is complex and difficult to measure due to incongruencies between clinical symptoms and disease states. Mucosal healing (MH) and transmural healing (TH) are increasingly used to measure clinical improvement in Crohn's disease, but definitions of MH and TH can vary across studies, and their relationship to long-term outcomes is not clear. To address this knowledge gap, we performed a systematic literature review (SLR) to examine studies measuring MH and TH in Crohn's disease. Database records from 2012 to 2022 were searched for real-world evidence and interventional studies that reported the association of MH or TH with clinical, economic, or quality of life outcomes of adult patients with Crohn's disease. A total of 46 studies were identified in the systematic literature review, representing a combined patient population of 5530. Outcomes of patients with MH were reported by 39 studies; of these, 14 used validated scales for endoscopic assessment. Thirteen studies reported outcomes of patients with TH. Among studies that examined the outcomes of patients with and without MH or TH, patients with healing generally experienced improved clinical outcomes and reduced healthcare resource utilization, including fewer hospitalizations and surgeries and improved rates of clinical remission. This was especially true for patients with TH. Mucosal and transmural healing are associated with positive long-term outcomes for adult patients with Crohn's disease. The adoption of standardized measures and less invasive assessment tools will maximize the benefits of patient monitoring.

Efficacy and safety of risankizumab by baseline corticosteroid use and achievement of corticosteroid-free clinical and endoscopic outcomes in patients with moderately to severely active Crohn's disease.

Risankizumab is efficacious and well tolerated in adults with moderately to severely active Crohn's disease (CD). To evaluate the corticosteroid-sparing effect of risankizumab in CD. During the 12-week induction period, patients maintained stable baseline corticosteroid doses, up to 20 mg/day prednisone or equivalent. At week 0 of maintenance, a mandatory corticosteroid taper was started. This post hoc analysis evaluated corticosteroid-free clinical and endoscopic outcomes at week 52 of maintenance; safety was also assessed. Of 889 patients randomised to induction with risankizumab 600 mg or placebo, 285 (32.1%) were taking baseline concomitant corticosteroids. Week 12 clinical remission and endoscopic response rates were greater for risankizumab 600 mg versus placebo, regardless of concomitant corticosteroid use. At week 52, 66.7%, 50.0% and 41.2% of patients taking risankizumab 180 mg, risankizumab 360 mg and (withdrawal) placebo, respectively, discontinued corticosteroids. Week 52 corticosteroid-free clinical remission per stool frequency/abdominal pain score (risankizumab 180 mg [42.7%] or 360 mg [49.8%]; [withdrawal] placebo [39.0%]), corticosteroid-free clinical remission per Crohn's Disease Activity Index (risankizumab 180 mg [51.0%] or 360 mg [49.5%]; [withdrawal] placebo [40.2%]), and corticosteroid-free endoscopic response (risankizumab 180 mg [44.6%] or 360 mg [44.7%]; [withdrawal] placebo [20.7%]) rates were greater for risankizumab than placebo. Adverse event rates were generally similar,regardless of baseline corticosteroid use. Efficacy of risankizumab 600 mg induction therapy was independent of concomitant corticosteroid use. Risankizumab 180 and 360 mg maintenance therapy yielded high rates of corticosteroid-free clinical and endoscopic outcomes at week 52.

Risankizumab for Ulcerative Colitis

The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135.

Budesonide Versus Mesalamine in Microscopic Colitis: A Comparative Meta-analysis of Randomized Controlled Trials.

Microscopic colitis (MC) is an inflammatory bowel disease of autoimmune origin that causes chronic watery diarrhea. Medications, including budesonide, mesalamine, loperamide, cholestyramine, and bismuth subsalicylate, are first-line therapies. Meanwhile, azathioprine, 6-mercaptopurine, and methotrexate are indicated for refractory MC. We aim to assess the efficacy and safety of budesonide compared with mesalamine for induction of remission in MC patients. We searched the Cochrane Library, Scopus, Web of Science, and PubMed for relevant clinical trials comparing either mesalamine or budesonide with a control group. We included the following outcomes: clinical remission (3 or fewer stools/day), daily stool weight, daily stool frequency, number of patients with clinical response <50% in the disease activity, and daily stool consistency. Safety end points included: any adverse event, serious adverse events, any adverse event-related discontinuation, abdominal discomfort, constipation, flatulence, nausea, dizziness, headache, bronchitis, nasopharyngitis, and depression. We conducted a meta-analysis model using the generic inverse variance method and performed a subgroup analysis based on the intervention administered. Nineteen randomized clinical trials were included. We found that after 6 weeks of follow-up, budesonide is associated with increased clinical remission rates compared with mesalamine [RR=2.46 (2.27, 2.67), and RR=2.24 (1.95, 2.57), respectively]. However, the test of subgroup difference revealed that the difference is not significant (P=0.25). After 8 weeks of follow-up, budesonide showed significantly higher clinical remission rates than mesalamine RR=2.29 (2.14, 2.45), and RR=1.7 (1.41, 2.05), respectively (P=0.003). Regarding the daily stool weight, patients in the budesonide group showed nonsignificant less stool weight [MD=-351.62 (-534.25, -168.99)] compared with mesalamine [MD=-104.3 (-372.34, 163.74)], P=0.14. However, daily stool frequency was significantly less in the budesonide group compared with mesalamine (P<0.001). Budesonide is associated with a significantly lower incidence of adverse events compared with mesalamine (P=0.002). Analysis of other safety endpoints was not significant between both groups. Budesonide was found to be better than mesalamine in MC patients in terms of clinical remission rate, especially after 8 weeks of follow-up. Budesonide also showed less incidence of adverse events. There is an urgent need for randomized, double-blinded clinical trials to provide direct and reliable evidence.

Early resolution of bowel urgency by budesonide foam enema results in improved quality of life in patients with ulcerative colitis: a multicenter prospective observational study.

Bowel urgency is an important symptom for quality of life determination in patients with ulcerative colitis (UC). Few clinical studies have focused on bowel urgency as an efficacy endpoint. Budesonide foam enema has shown efficacy for clinical and endoscopic improvement in mild-to-moderate UC. We evaluated the improvement of clinical symptoms (bowel urgency), safety, and treatment impact of twice-daily budesonide foam enema on the quality of life in patients with UC. This open-label, multicenter, prospective observational study comprised a 4-week observation period assessing the effectiveness and safety of twice-daily budesonide foam enema. Mild-to-moderate UC patients who had bowel urgency were included. Patients collected data daily in an electronic patient-reported outcome system or logbooks. The primary endpoint was the rate of resolution of bowel urgency at the end of the 4-week observation period. The rate of bowel incontinence was also assessed. Sixty-one patients were enrolled. Of patients with a final evaluation, the rate of resolution of bowel urgency was 58.5% (31/53; 95% confidence interval, 44.1%-71.9%). Bowel urgency decreased over time, with a significant difference observed on day 7 versus day 0. Bowel incontinence showed a decreasing trend from day 5, with a significant difference confirmed on day 12 versus day 0. The clinical remission rate was 64.4% (38/59; 95% confidence interval, 50.9%-76.4%). One adverse event not related to budesonide rectal foam occurred. The findings suggest that bowel urgency can be improved early with twice-daily budesonide foam enema. No new safety signals were observed.

An international multicentre study of SwiTching from Intravenous to subcutaneous inflixiMab and vEdolizumab in inflammatory bowel diseases: The TIME study.

Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel diseases (IBDs). Our aim was to evaluate the effectiveness of switching from intravenous (IV) to SC formulations of IFX and VDZ in IBDs. This multicentre, retrospective study collected data of adult patients with Crohn's disease (CD) or ulcerative colitis (UC) switched to SC IFX or VDZ. The primary endpoint was clinical remission at 12 months stratified based on timing of switch. A composite endpoint consisting of therapy discontinuation, reverse-switch, need for steroids, and drug optimization was evaluated. A multivariate analysis investigated the association between patients' characteristics and outcomes. Two hundred and thirty-one patients (59% UC, 53% male, mean age 44 ± 15 years, 68% IFX) from 13 centres were included. The switch occurred at Week 6 in a third of cases (36%). Median time to switch was 13 months. Most patients switched to SC IFX and VDZ were in clinical remission at 3 (87% and 77%), 6 (86% and 83%) and 12 (63% and 60%) months. In the multivariate analysis, there was no difference in clinical remission rate at 12 months; however, patients switched at Week 6 had a higher rate of experiencing any therapeutic changes at 3 (false discovery rate (FDR) = .002), 6 (FDR <1 × 10-10) or 12 months (FDR = .08). Clinical disease activity at baseline (only in UC) (FDR = .07) and previous exposure to biologics (FDR = .001) were risk factors for composite endpoint at 6 and 12 months. SC IFX and VDZ are effective in daily clinical practice in IBD patients. Switching patients in remission reduces the risk of negative outcomes.

Real-life effectiveness and safety of vedolizumab in moderate-to-severe ulcerative colitis: A single-center experience in Northern China.

Vedolizumab (VDZ), a monoclonal antibody to α4β7 integrin, is available for patients with moderate-to-severe ulcerative colitis (UC). This study planned to assess the real-world effectiveness and safety of VDZ for UC patients in Northern China. We enrolled patients with moderate-to-severe UC who underwent VDZ induction therapy from March 2021 to November 2022 at the Affiliated Hospital of Qingdao University. The primary outcome was clinical remission at weeks 14 and 52 after the initial VDZ therapy. Overall adverse events and risk factors associated with loss of response (LOR) were also evaluated. Seventy-three UC patients receiving VDZ therapy were included in this study. The rates of clinical response, clinical remission, and steroid-free clinical remission were 69.9%, 39.7%, and 34.2% at week 14 and 90.5%, 66.7%, and 64.4% at week 52, respectively. The mucosal remission rates were 37.5% (18/48) at week 14 ± 8 and 27.3% (9/33) at week 52 ± 16, while only 2 and 3 patients achieved mucosal healing at weeks 14 ± 8 and 52 ± 16, respectively. Of the UC patients, 23.3% experienced adverse events associated with VDZ, most of which were mild and self-limiting. Until the last follow-up, 37 of 73 UC patients experienced LOR during the maintenance period. Patients with a higher ulcerative colitis endoscopic severity index (UCEIS), partial Mayo scores (PMS), or hemoglobin below 120 g/L at baseline were more likely to experience LOR after VDZ induction therapy. VDZ is an effective and safe agent for patients with moderate-to-severe UC in Northern China. A high baseline UCEIS, PMS, or hemoglobin < 120 g/L may be an independent risk factor for LOR during the maintenance period.

Targeted surgery combined with postoperative medical therapy for residual disease for severe and multifocal Crohn disease

BackgroundIn patients with multifocal intestinal Crohn disease requiring surgery for complication or uncontrolled disease, resection of all the lesions may lead to diarrhea and malnutrition. MethodsThis is a single-center retrospective review of all patients undergoing targeted surgery for multifocal Crohn disease with at least one residual Crohn disease location left behind. The primary endpoint was the rate of insufficient control of residual Crohn disease lesions requiring redo-surgery targeting these lesions. The rate of clinical remission defined by Harvey–Bradshaw index <4 was studied over time. ResultsFrom January 2012 to August 2022, among 320 patients undergoing surgery for intestinal Crohn disease, 30 met all criteria. Before surgery, patients had received a mean of 3 medical treatment lines; 83% (n = 25) had a clinically active Crohn disease (Harvey–Bradshaw index ≥4). Surgery consisted in ileocolonic (n = 14;47%), small bowel (n = 5;17%) or colonic resection (n = 12;40%) and strictureplasty (n = 4;13%). Operative mortality was nil. Overall postoperative and severe morbidity rates were 15 of 30 (50%) and 3 of 30. Residual lesions were in the small bowel (n = 15;50%), the colon (n = 16;53%), and/or the rectum (n = 16;53%). Twenty-five patients (83%) had postoperative medical therapy. Median follow-up was 65. Six patients (20%) required reoperation for insufficient control of residual lesions at index surgery after a mean of 98 ± 8 months. The clinical remission rate increased from 17% before surgery to 59% at 6–12 months and 71% at 24 months. ConclusionIn patients with multifocal Crohn disease, surgery targeted to severe and complicated lesions combined with postoperative medical treatment is a safe and effective strategy.