Meta-analysis: Persistence of advanced therapies in the treatment of inflammatory bowel disease.

BACKGROUND: The expanding options in advanced therapies for ulcerative colitis (UC) and Crohn's disease (CD) present challenges in treatment selection. Persistence analysis assesses drug durability in real-world settings, acting as a surrogate marker for medication efficacy and tolerance. Unlike traditional comparative studies, persistence analysis provides insights extending beyond the initial year of treatment. AIM: To provide real-world evidence on treatment effectiveness, tolerability and preferences of physicians and patients regarding various advanced therapies for IBD. METHODS: We conducted a systematic review of observational studies up to March 2023 assessing advanced therapies' persistence in UC and CD. Advanced therapies under examination included infliximab, adalimumab, vedolizumab, ustekinumab, golimumab, certolizumab and tofacitinib. We pooled the persistence of each agent and conducted a meta-analysis to compare the persistence of newer agents with traditional TNF inhibitors (TNFi)-specifically infliximab and adalimumab. RESULTS: Among 63 observational studies, vedolizumab had the highest 1-year persistence in UC (73.8%, 95% CI: 70.0%-77.6%) and ustekinumab in CD (77.5%, 95% CI: 72.9%-82.1%). Compared to TNFi, vedolizumab demonstrated increased persistence with a relative risk (RR) of 1.30 (95% CI: 1.19-1.41) for UC and 1.14 (95% CI: 1.09-1.20) for CD at 1 year, while ustekinumab demonstrated a RR of 1.15 (95% CI: 1.07-1.23) for CD at 1 year. Vedolizumab exhibited sustained increased persistence in UC over 2 years compared to TNFi (RR: 1.33, 95% CI 1.14-1.54). CONCLUSION: This meta-analysis highlights the superior persistence of ustekinumab and vedolizumab over TNFi, and offers valuable insights for clinicians navigating the challenging landscape of UC and CD therapeutic choices.

Ustekinumab effectiveness in Crohn's disease with lesions in the intestines.

Ustekinumab is prescribed for the treatment of patients with steroid-resistant moderate to severe Crohn's disease. We investigated its clinical outcome in patients with small and large intestinal lesions. Patients who were newly administered ustekinumab between March 2014 and December 2020 at Hamamatsu University Hospital were included in the study. The primary endpoint was Crohn's disease activity index score at baseline and weeks 8, 24, and 48 after the initiation of treatment, and secondary endpoints were albumin, hemoglobin, and C-reactive protein at these time points. Ustekinumab treatment retention was examined in both groups; the 2 groups were compared using the Friedman test, Mann-Whitney U test, or Fisher exact test. Overall, Crohn's disease activity index scores improved between baseline and 48 weeks, but the difference was not significant. However, there was a significant improvement between baseline and 48 weeks in patients with lesions in the small intestine only. Overall, patients showed significant improvement in albumin levels between baseline and 48 weeks but not in C-reactive protein or hemoglobin levels. When limited to patients with lesions in the small intestine, albumin and hemoglobin levels showed significant improvement. Both types showed high rates of treatment retention, although there was no significant difference. Ustekinumab appears to be a safe and effective treatment option that may be particularly effective in patients with lesions in the small intestine only.

[Pouchitis showed complete response to ustekinumab].

Pouchitis is the most common long-term complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis. Although several agents, including probiotics, steroids, and immunomodulators, have been used, the treatment of pouchitis remains challenging. Owing to the proven efficacy of biological therapy in inflammatory bowel disease, there is now growing evidence suggesting the potential benefits of biological therapy in refractory pouchitis. Here, we report the case of a 64-year-old woman with pouchitis due to ulcerative colitis who was successfully treated with ustekinumab (UST). The patient developed ulcerative pancolitis at the age of 35. Total colectomy and IPAA with J-pouch anastomosis were performed when the patient was 47 years old. Ileotomy closure was performed 6 months later. Postoperatively, the patient developed steroid-dependent pouchitis. Three years later, she developed steroid-induced diabetes. The patient has been taking 3mg of steroid for 20 years;therefore, her lifetime total steroid dose was 21g. The patient had over 20 episodes of bloody diarrhea a day. The last pouchoscopy in 20XX-9 revealed inflammatory stenosis with deep ulcerations of the afferent limb just before the ileoanal pouch junction. In July 20XX, when we took over her treatment, the policy of treatment was to withdraw her from steroids. Pouchoscopy revealed a widened but still tight afferent limb through which the scope could easily pass, and the ileoanal pouch still showed erosive ileitis without ulcers. Thiopurine administration and steroid tapering were initiated. Steroid tapering increased the erythrocyte sedimentation rate (ESR). As ESR increased, her arthritis exacerbated. Six months after the end of steroid administration, the patient consented to UST treatment. On April 20XX+1, the patient received her first 260-mg UST infusion. At this point, she experienced 14-15 episodes of muddy bloody stools. She had no abdominal pain;however, she experienced shoulder pain. Gradually, UST affected both pouchitis and arthritis. UST treatment was continued at 90mg subcutaneously every 12 weeks without abdominal pain recurrence. Eight months after the first UST infusion, nonsteroidal anti-inflammatory drugs were no longer necessary for shoulder pain. Follow-up pouchoscopy performed 14 months after UST optimization revealed a normal afferent limb without ulcerations in either segment. Pouchitis remission was maintained for over 2 years.

[Clinical remission and transmural healing of ustekinumab in patients with Crohn's disease].

OBJECTIVE: To treat the Crohn's disease (CD) patients with ustekinumab (UST), to eva-luate their clinical and endoscopic remission, and to evaluate their transmural response (TR) and transmural healing (TH) condition using intestinal ultrasonography (IUS). METHODS: Retrospective analysis was made on patients diagnosed with CD in Peking University People's Hospital from January 2020 to August 2022, who were treated with UST for remission induction and maintenance therapy. All the patients were evaluated on both week 8 and week 16/20 after treatment, including clinical, biochemical indicators, colonoscopy and IUS examination. RESULTS: A total of 13 patients were enrolled in this study, including 11 males and 2 females. The minimum age was 23 years, the maximum age was 73 years and the mean age was 36.92 years. All the patients were in the active stage of disease before treatment, and the average Best Crohn's disease activity index (Best CDAI) score was 270.12±105.55. In week 8, the Best CDAI score of the patients decreased from 270.12±105.55 to 133.16±48.66 (t=4.977, P < 0.001). Eight patients achieved clinical remission while 5 patients remained in the active stage. Nine patients underwent colonoscopy evaluation. The average simple endoscopic score for Crohn's disease (SES-CD) score decreased from 10.71±7.14 before treatment to 6.00±7.81(t=2.483, P=0.048) in week 16/20. Four patients achieved endoscopic remission while 5 patients did not. In week 8, 5 patients achieved TR, 2 patients achieved TH, the other 6 patients did not get TR or TH. In week 16/20, 6 patients achieved TR, 3 patients achieved TH while the other 4 patients did not get TR or TH. There was no significant statistical difference in the TR effect of UST between small intestine and colon lesions (Fisher test, P > 0.999). The rate of UST transmural response in the patients who had had previous biological agent therapy was lower than those with no previous biological agent therapy, but there was no significant statistical difference (Fisher test, P=0.491). CONCLUSION: After treatment of UST, the clinical and endoscopic conditions of the CD patients had been improved, and some patients could achieve clinical remission and endoscopic remission. UST had good TR and TH effects on CD. TR might appear in week 8, and the TR effect increased in week 16/20. There was no significant statistical difference in the TR effect between small intestine and colon lesions. TR effect of UST was better in the patients who had no previous biological agent therapy than those who had had other biological agents, but the result had no significant statistical difference.

Biological treatment approach to inflammatory bowel disease is similar in academic and nonacademic centres - prime time for decentralisation of inflammatory bowel disease care?

BACKGROUND: With the increasing number of inflammatory bowel disease (IBD) patients, it is difficult to manage them within specialised IBD teams in academic medical centres: many are therefore treated in nonacademic IBD centres. It is unclear whether the time to introducing biologics is the same in both settings. AIM: We aimed to compare treatment approach with biologics in academic vs. nonacademic centres. METHODS: We analysed Slovenian national IBD registry data (UR-CARE Registry, supported by the European Crohn's and Colitis Organisation), which included 2 academic (2319 patients) and 4 nonacademic IBD (429 patients) centres. RESULTS: The disease phenotype was similar in both settings. In total, 1687 patients received 2782 treatment episodes with biologics. We observed no differences in treatment episodes with TNF-alpha inhibitors (60% vs. 61%), vedolizumab (24% vs. 23%), or ustekinumab (17% vs. 16%) in academic compared to nonacademic centres ( P  = 0.949). However, TNF inhibitors were less often the first biologic in academic centres (TNF inhibitors: 67.5% vs. 74.0%, vedolizumab: 20.3% vs. 17.9%, ustekinumab: 12.1% vs. 8.1%; P = 0.0096). Consequently, more patients received ustekinumab (29.8% vs. 18.3%) and vedolizumab (17.4% vs. 13.5%) and fewer TNF inhibitors (52.7% vs. 68.2%) for Crohn's disease in academic compared to nonacademic centres, with no such differences for ulcerative colitis. The time to initiation of the first biologic from diagnosis was short and similar in both settings (11.3 vs. 10.4 months, P  = 0.2). CONCLUSION: In this nationwide registry analysis, we observed that biological treatment choice was similar in academic and nonacademic settings. These findings support the decentralisation of IBD care.

Real-world clinical outcomes and healthcare costs in patients with Crohn's disease treated with vedolizumab versus ustekinumab in the United States.

OBJECTIVE: To compare real-world treatment persistence, dose escalation, rates of opportunistic or serious infections, and healthcare costs in patients with Crohn's disease (CD) receiving vedolizumab (VDZ) vs ustekinumab (UST) in the United States. METHODS: A retrospective observational study in adults with CD initiated on VDZ or UST on/after 26 September 2016, was performed using the IBM Truven Health MarketScan databases (1 January 2009-30 September 2018). Rates of treatment persistence, dose escalation, opportunistic or serious infection-related encounters, and healthcare costs per patient per month (PPPM) were evaluated. Entropy balancing was used to balance patient characteristics between cohorts. Event rates were assessed using weighted Kaplan-Meier analyses and compared between cohorts using log-rank tests. Healthcare costs were compared between cohorts using weighted 2-part models. RESULTS: 589 VDZ and 599 UST patients were included (172 [29.2%] and 117 [19.5%] were bio-naïve, respectively). After weighting, baseline characteristics were comparable between cohorts. No significant difference in rates of treatment persistence (12-month: VDZ, 76.5%; UST, 82.1%; p = .17), dose escalation (12-month: VDZ, 29.3%; UST, 32.7%; p = .97), or opportunistic or serious infection-related encounters were observed between VDZ and UST. Total mean healthcare costs were significantly lower for patients treated with VDZ vs UST (mean cost difference = -$5051 PPPM; p < .01). Findings were consistent in bio-naïve patients. CONCLUSIONS: In this real-world study, similar treatment persistence, dose escalation, and rates of opportunistic or serious infections were observed with VDZ- and UST-treated patients with CD. However, VDZ was associated with a significantly lower cost outlay for healthcare systems.

Crohn's disease (CD) causes inflammation in the digestive system. Vedolizumab (VDZ) and ustekinumab (UST) are therapies for patients with CD. Little is known about the clinical outcomes and healthcare costs of VDZ versus UST in the real world in the United States. We used health claims data and found that VDZ and UST had comparable real-world clinical outcomes. After 12 months of treatment, the proportions of patients with CD who stayed on treatment and those who needed to increase therapy dose were similar with VDZ and UST. The rate of infection was also similar between the two groups of patients. However, the monthly healthcare costs were $5051 less for patients treated with VDZ than with UST. This was mainly due to the lower cost of VDZ, which was almost half of that of UST. The lower treatment costs with VDZ may provide substantial savings for the healthcare system and patients specifically. Future cost-effectiveness studies on VDZ and UST are needed to aid treatment selection for patients with CD.

Short-term effectiveness and potential factors of ustekinumab based on real-world data in Chinese psoriasis patients.

BACKGROUND: As one of the most effective biologic treatments for psoriasis, the short-term effectiveness of ustekinumab has yet to be studied extensively. OBJECTIVE: The purpose of this study was to evaluate the short-term effectiveness and potential factors within four weeks after the first-dose ustekinumab treatment based on real-world data. METHODS: The study enrolled 98 patients with moderate-to-severe psoriasis, given ustekinumab 45 mg at week 0, week 4, and then every 12 weeks. Based on clinical data collected at baseline and week 4, we investigated the short-term effectiveness of ustekinumab after the first dose and potential factors associated with the treatment. For evaluation, we collected demographic information, body data, medical history, laboratory examination results, Psoriasis Area and Severity Index (PASI), body surface area (BSA), and dermatology life quality index (DLQI). Response rates were calculated based on the number of patients that achieved a 75/90/100% reduction in PASI (PASI 75/90/100), and the primary treatment goal was to achieve PASI 75. RESULTS: The response rates for PASI 75/90/100 at week 4 were 30.5%, 18.9%, and 16.8%, respectively. For PASI 75, the response rate was higher in patients without metabolic syndrome (MS) (without MS vs. with MS: 36.9% vs. 5.9%, p = 0.013); the serum triglyceride (TG) level was significantly lower in patients achieving PASI 75 (expressed as mean ± standard deviation, achieved vs. unachieved: 1.82 ± 1.79 vs. 3.59 ± 8.89, p = 0.010). For PASI 100, the response rates were higher in female patients (female vs. male: 26.3% vs. 10.5%, p = 0.044) and patients with a family history of psoriasis (with family history vs. without family history: 44.4% vs. 13.9%, p = 0.042). In addition, the possibility of achieving PASI 75/90/100 went up along with the serum high-density lipoprotein cholesterol (HDL-C) level (expressed as adjusted odds ratio < 95% confidence interval>: PASI 75: 28.484 < 2.035-248.419>, p = 0.011; PASI 90: 28.226 < 2.828-281.729>, p = 0.004; PASI 100: 12.175 < 1.876-79.028>, p = 0.009). CONCLUSION: In this study, nearly one-third of patients achieved PASI 75 after only the first-dose ustekinumab treatment. Sex, family history of psoriasis, MS, serum TG level might affect the short-term effectiveness, and serum HDL-C level may be a potential factor. The possibility of achieving treatment goals (PASI 75/90/100) at week 4 increased along with serum HDL-C levels.

Risk of serious infection associated with different classes of targeted therapies used in psoriatic arthritis: a nationwide cohort study from the French Health Insurance Database (SNDS).

OBJECTIVE: To assess the risk of serious infection associated with different targeted therapies for psoriatic arthritis (PsA) in real-world settings. METHODS: This nationwide cohort study used the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database to identify all adults with PsA who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib) from 1 January 2015 to 30 June 2021. The primary outcome was a serious infection (ie, requiring hospitalisation), in a time-to-event analysis using propensity score-weighted Cox models, with adalimumab as the comparator, estimating weighted HRs (wHRs) and their 95% CIs. RESULTS: A total of 12 071 patients were included (mean age 48.7±12.7 years; 6965 (57.7%) women). We identified 367 serious infections (3.0% of patients), with a crude incidence rate of 17.0 per 1000 person-years (95% CI, 15.2 to 18.7). After inverse propensity score weighting and adjustment for time-dependent covariates and calendar year, risk of serious infection was significantly lower for new users of etanercept (wHR 0.72; 95% CI, 0.53 to 0.97) or ustekinumab (wHR, 0.57; 95% CI, 0.35 to 0.93) than adalimumab new users. This risk was not statistically modified with the other targeted therapies. CONCLUSIONS: The incidence of serious infection was low for PsA patients who were new users of targeted therapies in real-world settings. Relative to adalimumab new users, this risk was lower among new users of etanercept and ustekinumab and unmodified for the other molecules.

Case report: Successful treatment of ulcerative colitis-related post-colectomy enteritis refractory to multiple therapies with ustekinumab.

Ulcerative colitis-related severe post-colectomy enteritis is a rare condition. A few cases have undergone successful treatment with corticosteroids, Cyclosporine, Azathioprine, and Infliximab. We aim to evaluate the treatment outcome of ustekinumab in this rare case. Here we describe a 56-year-old woman with post-colectomy enteritis refractory to multiple therapies. Finally, the patient was administered with ustekinumab treatment. Under monitoring, the feces volume of the patient decreased from 5000-7000 mL per day to 1700-2000 mL. Over a one-year follow-up period, the patient gradually gained body weight, with the stoma drainage of formed brown stool. And the villi of the small intestinal mucosa restore growth. To our knowledge, this is the first report that indicates ustekinumab could be a treatment selection for ulcerative colitis-related severe post-colectomy enteritis.

Research progress of Ustekinumab in the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic, recurrent gastrointestinal disorder with elusive etiology. Interleukin-12 (IL-12) and IL-23 have emerged as key proinflammatory mediators/cytokines in IBD pathogenesis. Ustekinumab (UST), targeting IL-12 and IL-23, has demonstrated promising efficacy and safety in the treatment of IBD. Recently, UST has become increasingly favored as a potential first-line treatment option. This review delineates UST's mechanism of action, its clinical applications in IBD, including the response rates, strategies for dose optimization for case of partial or lost response, and potential adverse events. This review aims to offer a comprehensive understanding of UST's role as a therapeutic option in IBD management.

Real-world effectiveness of ustekinumab and vedolizumab in TNF-exposed pediatric patients with ulcerative colitis.

OBJECTIVES: Vedolizumab (VDZ) and ustekinumab (UST) are second-line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti-TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti-TNF refractory UC. METHODS: We performed a propensity-score weighted regression analysis to compare corticosteroid-free clinical remission (CFCR) at 6 months from starting second-line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk. RESULTS: Our cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41-1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76-2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness. CONCLUSIONS: UST and VDZ are similarly effective for inducing clinical remission in anti-TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies.

Selection strategy of second-line biologic therapies in adult patients with ulcerative colitis following prior biologic treatment failure: Systematic review and meta-analysis.

BACKGROUND: Optimizing second-line biologic therapies for adult ulcerative colitis (UC) post first-line failure is essential. OBJECTIVE: Compare second-line biologic therapy efficacy in adult UC patients with prior treatment failure. METHODS: A comprehensive search of electronic databases up to May 2023 was conducted to assess second-line biologic therapy efficacy using a random effects model. Parameters analyzed included clinical remission rate, clinical response rate, mucosal healing rate, annual discontinuation rate, and colectomy rates. RESULTS: Forty-three research papers were analyzed. Clinical remission rates for second-line biologics were ranked at 6-14 weeks: Infliximab (30%) was followed by Vedolizumab (29%), Ustekinumab (27%), and Adalimumab (19%). At 52-54 weeks, the order shifted, with Vedolizumab (35%) followed by Infliximab (32%), Ustekinumab (31%), and Adalimumab (26%). The mucosal healing rate was 21%, ranked as: Infliximab (31%), Vedolizumab (21%), Adalimumab (21%), and Ustekinumab (14%). The annual discontinuation rate stood at 20%, with Adalimumab (25%), Vedolizumab (18%), Infliximab (17%), and Ustekinumab (16%). Discontinuation rates due to primary failure (PF), secondary failure (SF), and adverse events (AE) were 6%, 12%, and 3%, respectively. The annual colectomy rate was 9%, with Adalimumab (15%) followed by Vedolizumab (10%), Ustekinumab (9%), and Infliximab (5%), and colectomy rates of 10% due to PF, 12% due to SF, and 4% due to AE. CONCLUSION: For UC patients with first-line treatment failure, it is recommended to prioritize infliximab or vedolizumab as second-line biologic therapies, while avoiding adalimumab as the primary choice. Further clinical trials are necessary to assess ustekinumab efficacy accurately.

Clinical use of biologics for Crohn's disease in adults: lessons learned from real-world studies.

INTRODUCTION: The therapeutic armamentarium for managing Crohn's disease (CD) has expanded significantly in recent decades. Several biologics with three different mechanisms of action [anti-tumor necrosis factor (TNF)-α, anti-integrin α4ß7, and anti-IL 12/23] are currently available to manage CD. AREA COVERED: This narrative review aims to summarize the most significant efficacy and safety data on the use of infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ) and ustekinumab (UST) for the treatment of CD obtained from studies conducted in the real world (RW), compared to the results of randomized clinical trials (RCTs). EXPERT OPINION: RW studies reported that biologic agents included in this analysis have higher remission rates and lower adverse event rates than findings from RCTs for treating patients with CD. All biological agents have proven effective and safe in RW studies, even when using biosimilars or switching to subcutaneous administration of the molecules for which they are available. Finally, anti-TNF-α agents, particularly IFX, have a higher rate of adverse events (AEs) than VDZ and UST. Therefore, patients at higher risk of AEs may benefit from other biologics than anti-TNF-α. However, further long-term RW studies are needed to confirm these findings.

Machine learning using clinical data at baseline predicts the medium-term efficacy of ustekinumab in patients with ulcerative colitis.

Predicting the therapeutic response to biologics before administration is a key clinical challenge in ulcerative colitis (UC). We previously reported a model for predicting the efficacy of vedolizumab (VDZ) for UC using a machine-learning approach. Ustekinumab (UST) is now available for treating UC, but no model for predicting its efficacy has been developed. When applied to patients with UC treated with UST, our VDZ prediction model showed positive predictive value (PPV) of 56.3% and negative predictive value (NPV) of 62.5%. Given this limited predictive ability, we aimed to develop a UST-specific prediction model with clinical features at baseline including background factors, clinical and endoscopic activity, and blood test results, as we did for the VDZ prediction model. The top 10 features (Alb, monocytes, height, MCV, TP, Lichtiger index, white blood cell count, MCHC, partial Mayo score, and CRP) associated with steroid-free clinical remission at 6 months after starting UST were selected using random forest. The predictive ability of a model using these predictors was evaluated by fivefold cross-validation. Validation of the prediction model with an external cohort showed PPV of 68.8% and NPV of 71.4%. Our study suggested the importance of establishing a drug-specific prediction model.

Comparative effectiveness and safety of ustekinumab at different intervals of maintenance phase in inflammatory bowel disease: a systematic review and meta-analysis.

Ustekinumab has two alternative drug maintenance intervals for inflammatory bowel disease (IBD), every 8 weeks (Q8W) and every 12 weeks (Q12W). The current study aimed at evaluating the comparative efficacy and safety of the two maintenance intervals in patients with IBD. A systematic search on PubMed, Web of Science, Cochrane Library, and EMBASE was carried out. The relative risk (RR) was pooled for efficacy and safety outcomes between the two intervals at various follow-up time points, categorized as short term (less than 44 weeks), medium term (about 92 weeks), and long term (about 152 weeks). A total of 14 studies with 1448 patients were included. Q8W didn't result in a remarkably higher proportion of clinical remission compared to Q12W at short term (RR, 0.99; 95% CI, 0.83-1.16), medium term (RR, 1.05; 95% CI, 0.91-1.20), and long term (RR, 1.07; 95% CI, 0.91-1.26). Similarly, no substantial differences exist at short term in clinical response (RR, 1.00; 95% CI, 0.85-1.17), endoscopic remission (RR, 0.97; 95% CI, 0.26-3.69), and histologic improvement (RR, 1.13; 95% CI, 0.93-1.36) between the two intervals. For safety outcomes, the RR values for any adverse events in the short, medium, and long term were 1.10 (95% CI, 1.00-1.21), 1.14 (95% CI, 1.08-1.20), and 1.12 (95% CI, 1.07-1.17) for Q8W versus Q12W. Finally, we conclude that ustekinumab maintenance therapy administered every 8 and 12 weeks showed similar effectiveness in achieving efficacy outcomes in IBD patients, and most safety outcomes were significantly better for Q12W during the maintenance phase.

Emerging biologic therapies for systemic lupus erythematosus.

PURPOSE OF REVIEW: The approval of belimumab and anifrolumab has expanded the scope of treatment for systemic lupus erythematosus (SLE) patients. However, many patients remain refractory to currently available therapies and suffer from drug toxicities. This review will discuss approved and target-specific therapeutics in development that bring hope for better SLE treatments. RECENT FINDINGS: Since the last review on this subject in the journal, the FDA has approved anifrolumab and belimumab for SLE and lupus nephritis (LN), respectively. A fully humanized anti-CD20, obinutuzumab, met the primary end point in a phase II trial in LN. A Tyk2 inhibitor, deucravacitinib, and an antibody targeting plasmacytoid dendritic cells, litifilimab, met the primary end point in phase II trials in SLE and cutaneous lupus erythematosus (CLE). Ustekinumab and baricitinib met the primary end point in phase II but not in phase III trials. SUMMARY: While many drug candidates which met the end points in phase II trials have failed phase III trials, the number of target-specific therapies for SLE has continued to expand.

Therapeutic Drug Monitoring for Biologic and Small-Molecule Therapies for Inflammatory Bowel Disease.

Background: Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, necessitates long-term medical therapy to manage symptoms and prevent complications. Therapeutic drug monitoring (TDM) has emerged as a strategy to optimize treatment efficacy, particularly with anti-tumour necrosis factor (anti-TNF) alpha drugs. This review explores the role of TDM for non-anti-TNF advanced therapies in IBD, focusing on vedolizumab, ustekinumab, tofacitinib, upadacitinib, risankizumab and ozanimod. Methods: The literature search, conducted through OVID (Medline) and PubMed, delves into proactive versus reactive TDM, timing of monitoring and methods for measuring drug levels and anti-drug antibodies. Results: While ustekinumab and vedolizumab exhibit exposure-response relationships, consensus on target levels and the role of TDM adjustments remains elusive. Limited data on risankizumab suggest a dose-dependent response, while for small molecule therapies (janus kinase inhibitors and ozanimod), the absence of real-world data and commercially available TDM tools pose challenges. Conclusion: At present, with the available data, there is a limited role for TDM in non-anti-TNF biologic and small-molecule therapies. This review underscores the need for further research to delineate the utility of TDM in guiding treatment decisions for these agents.