Use Of Ustekinumab Research Articles

Association between nutritional status assessed by body mass index and Crohn's disease phenotype: A Nation-wide analysis

Background & aimsIncidence of obesity and Crohn's disease (CD) is increasing globally. Therefore, understanding any associations between adiposity and disease phenotype is crucial. We aimed explore the relationship between nutritional status measured by body mass index (BMI) and phenotypes of CD using a large national recallable data set. MethodsUsing National Institute for Health and Care Research-IBD Bioresource data base, we retrospectively assessed the relationship between BMI and stenosing CD by logistic regression. BMI was the primary variable of interest; CD behaviour was the dependent variable; stenosing CD was the primary outcome. Confounders were adjusted for in a multivariate model. Results8797 patients diagnosed between 1942 and 2020 were included. Mean overall BMI was 26.3 kg/m2 (SD5.5). 52.7 % had a BMI ≥25 kg/m2 (mean 30.2 kg/m2, SD 4.5). Majority had inflammatory CD (62.9 %) followed by stenosing (25.1 %) and penetrating CD (12 %). Stenosing and penetrating phenotypes were more common in the <25 kg/m2 BMI group (50.7 %, 50.3 % respectively) p < 0.001. Colonic disease location was more common (27.8 % vs 24.3 %, p = 0.001) in patients with high BMI. On univariate analysis, stenosing disease was positively associated with ileal disease location, disease duration, previous surgery, use of infliximab, ustekinumab, vedolizumab, adalimumab and azathioprine but negatively associated with BMI (OR 0.98, 95%CI [0.968–0.99]). On multivariate analyses, BMI remained negatively associated with stenosing CD (OR 0.98, 95%CI [0.97–0.99]); ileal disease location (OR 3.69, 95%CI [3.22–4.24]), adalimumab (OR 1.47, 95%CI [1.30–1.66]), ustekinumab usage (OR 1.51, 95%CI [1.14–2.01] and azathioprine (OR 1.35, 95%CI [1.19–1.53]). ConclusionsAfter multivariate analyses, BMI, ileal disease location and biologic use was negatively associated with a stenosing disease phenotype. This might reflect a change in eating behaviour due to persistent postprandial symptoms related to stenosing disease. Large longitudinal studies are needed to investigate any possible temporal relationship between the obesogenic state and intestinal fibrosis.

Challenges in Managing Cytomegalovirus Colitis in a Complex Case of Ulcerative Colitis With Hyposplenism and Ustekinumab Therapy

ABSTRACT Colitis secondary to cytomegalovirus (CMV) infection is a recognized complication in patients with ulcerative colitis. This case report details a patient with a background of ulcerative colitis with resultant hyposplenism on ustekinumab therapy who presented with CMV colitis. The presence of hyposplenism with the use of ustekinumab resulted in challenges when treating the CMV infection due to the absence of immune response and required individual tailoring of therapy with higher doses of ganciclovir and valganciclovir according to trough level measurement.

Efficacy and safety of mirikizumab compared with currently approved biologic drugs for the treatment of ulcerative colitis: A systematic review and network meta-analysis.

Ulcerative colitis (UC) is a serious health problem that requires a constant need to identify new effective drugs. The aim of this study was to assess the efficacy and safety of mirikizumab compared with other biologic drugs approved for the treatment of moderately to severely active UC. This systematic review with frequentist network meta-analysis (NMA) included randomized controlled trials (RCTs) that evaluated the use of adalimumab, golimumab, infliximab, mirikizumab, vedolizumab, and ustekinumab compared with placebo or with another approved biologic drug. The NMA was conducted using the netmeta R software package. The P score was used to determine the treatment ranking. A total of 14 RCTs were included in the analysis. No significant differences were observed in the incidence of clinical response and remission between mirikizumab and other drugs. Mirikizumab was superior to placebo for clinical response (induction: odds ratio [OR] = 2.38; 95% confidence interval [CI]: 1.63-3.48; maintenance: OR = 3.31, 95% CI: 1.59-6.89) and remission (induction: OR = 2.09, 95% CI: 1.20-3.63; maintenance: OR = 2.96; 95% CI: 1.62-5.40). The probability plot indicated that infliximab might be the most effective option in terms of both clinical response and remission (P score, 0.8971 and 0.8814, respectively) in induction phase. No significant differences were noted between the studied drugs in any adverse events (AEs), serious AEs (SAEs) and infections for the induction phase, and in any AEs, infections and serious infections for the maintenance phase. The drugs differed in terms of discontinuation due to AEs (induction and maintenance phases) as well as SAEs and serious infections (maintenance phase). Mirikizumab did not differ from other biologics in terms of clinical response and remission for both induction and maintenance phases in patients with UC. Mirikizumab during the induction phases achieved rank 3 for clinical response and rank 5 for clinical remission. Therefore, it represents a valuable treatment option. The lack of significant differences in the risk of AEs and SAEs suggests that mirikizumab has a similar safety profile to the other drugs.

The Use of Immunomodulators, Biologic Therapies, and Small Molecules in Patients With Inflammatory Bowel Disease and Solid Organ Transplant.

Patients with inflammatory bowel diseases (IBDs) may require solid organ transplants (SOTs) for multiple reasons, making its prevalence slightly higher than the general population. Although immunosuppression used in SOT may help control IBD-related inflammation, many patients still require additional immunosuppressive medications. We aim to assess the effectiveness and safety of the combination of SOT-related immunosuppression and IBD medications in patients with liver, kidney, or heart transplantation. We conducted a clinical review using PubMed, Scopus, MEDLINE, Embase, and Google Scholar databases for our search. We included data from systematic reviews, meta-analyses, case series, and case reports to assess the safety, effectiveness, and side effect profile of immunomodulators, biologic therapies, and small molecules in patients with SOT. Our review encompassed 25 liver, 6 kidney, and 1 heart transplant studies involving patients with IBD. Common liver transplant immunosuppressants included tacrolimus, mycophenolate mofetil, cyclosporine, and steroids. Anti-TNF agents, widely used in all SOT types, showed no significant safety issues, though infections and malignancies were noted. Patients with liver transplant on tacrolimus responded well to anti-integrins and ustekinumab without major complications. For kidney transplants, cyclosporine and tacrolimus were prevalent, and their combination with anti-TNF or ustekinumab was generally safe, with rare reports of malignancy or infection. Hence, the use of anti-TNF, anti-integrin agents, and ustekinumab appears to be safe in patients with SOT, regardless of their transplant related immunosuppression. More studies are needed in patients with kidney and heart transplants and in patients treated with small molecules for their IBD.

Safety and Effectiveness of Ustekinumab for Crohn's Disease With Perianal Manifestations: Ad hoc Analysis Data From 1-Year Post-Marketing Surveillance Study in Japan.

Crohn's disease (CD) is an immune-mediated inflammatory disorder of the gastrointestinal tract with perianal disease being one of the challenging possible manifestations. Here, we report, an ad hoc analysis of the safety and effectiveness of 1-year use of ustekinumab (UST) for CD in patients with perianal manifestations using post-marketing surveillance (PMS) data in Japan. Among 341 patients enrolled in the PMS, 229 and 224 patients who had baseline Crohn's Disease Activity Index (CDAI) data used for evaluating perianal manifestations were included in the safety and efficacy analysis sets, respectively. Incidence of adverse drug reactions, clinical remission, the mean or its change in CDAI scores, and CDAI items were evaluated through week 52 in the presence or absence of perianal manifestations at baseline. The prevalence of perianal manifestations was also described. Comparing patients with and without baseline perianal manifestations at week 52, there was no difference in ADR incidence (9.1% [n = 66] vs. 15.3% [n = 163]), no difference in clinical remission (68.3% vs. 59.9%; P = 0.269), and decreased mean change of CDAI score (-82.9 [n = 60] vs. -68.8 [n = 137]). The proportion of patients with perianal manifestations decreased after UST treatment in both biologics-naïve patients (23.5% [n = 4/17]) and patients who had received biologics (35.0% [n = 14/40]) at week 52. In Japanese clinical practice, UST is safe and effective in CD patients with and without perianal manifestations. The therapy might be also beneficial in those with manifestations regardless of prior use of other biologics.

STEP-CD study: ustekinumab use in paediatric Crohn's disease-a multicentre retrospective study from paediatric IBD Porto group of ESPGHAN.

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause. Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

Evidence-Based Approach to Chronic Antibiotic Refractory Pouchitis: A Review.

Chronic antibiotic refractory pouchitis after restorative proctocolectomy with IPAA, characterized by at least 4 weeks of pouchitis symptoms that have not responded to standard antibiotic therapy, presents a therapeutic challenge for patients and health care providers. The aim of this narrative review was to summarize the current evidence regarding the management of chronic antibiotic refractory pouchitis. Studies were identified through a search of the PubMed database from the National Library of Medicine. We included case series, cohort studies, randomized controlled trials, and systematic reviews with meta-analyses that addressed chronic antibiotic refractory pouchitis management, with prioritization of data published within the past 3 to 5 years. Studies examining pharmacologic and select nonpharmacologic interventions were included. Outcomes measures included clinical, endoscopic, and histologic end points. Mesalamine has demonstrated efficacy in symptom improvement but no improvement in quality of life. Budesonide has demonstrated high rates of clinical remission that have mostly been sustained in a small number of patients. Anti-tumor necrosis factor therapies have demonstrated efficacy in reaching clinical and even endoscopic end points, although rates of treatment discontinuation were not insignificant. Limited evidence is encouraging for the use of ustekinumab in achieving clinical response. Data for vedolizumab are favorable across clinical, endoscopic, and histologic end points, including one of the only randomized, placebo-controlled trials. Nonmedication therapies, including hyperbaric oxygen therapy and fecal microbiota transplant, have undergone limited evaluation, and concerns about the ultimate accessibility of these therapies remain. Overall, studies assessing therapeutic options for chronic antibiotic refractory pouchitis are mostly limited to case series and retrospective studies with small sample sizes. Biologic therapies have demonstrated efficacy in the management of chronic antibiotic refractory pouchitis and offer a steroid-sparing option for refractory disease. Nonpharmacologic therapies, including hyperbaric oxygen and fecal microbiota transplant, require further exploration. See video from symposium .

Use of Biologics for the Treatment of Inflammatory Conditions of the Pouch: A Systematic Review.

Patients with medically-refractory ulcerative colitis or advanced neoplasia are often offered an ileal-pouch-anal anastomosis to restore bowel continuity. However, up to 50% of patients can suffer from inflammatory conditions of the pouch, some of which require biological therapy to treat. The aim of this study was to determine the efficacy of each biological agent for the treatment of inflammatory conditions of the pouch. A comprehensive literature search was performed in the major databases from inception through February 11, 2020, for studies assessing the efficacy of biologics in chronic antibiotic-refractory pouchitis (CARP) and Crohn's disease (CD) of the pouch. Both prospective and retrospective studies were included. The primary outcomes of interest were complete and partial responses were defined within each study. χ 2 test was used to compare variables. Thirty-four studies were included in the systematic review and meta-analysis. Sixteen studies (N=247) evaluated the use of infliximab (IFX), showing complete response in 50.7% and partial response in 28.1% for CARP, and complete response in 66.7% and partial response in 20% for CD of the pouch. Seven studies (n=107) assessed the efficacy of adalimumab. For CARP, 33.3% of patients had a complete response, and 38.1% had a partial response, whereas for CD of the pouch, 47.7% experienced a complete response, and 24.6% had a partial response. Three studies (n=78) reported outcomes with the use of ustekinumab, showing 50% complete response and 3.8% partial response for CARP. For the CD of the pouch, 5.8% had a complete response and 78.8% had a partial response. Seven studies (n=151) reported the efficacy of vedolizumab, showing 28.4% complete response and 43.2% partial response in patients with CARP, whereas 63% of patients experienced partial response in CD of the pouch. IFX had higher rates of complete response in CARP compared with adalimumab ( P =0.04) and compared with vedolizumab ( P =0.005), but not compared with ustekinumab ( P =0.95). There were no new safety signals reported in any of the studies. Biologics are safe and efficacious in the treatment of chronic, refractory inflammatory conditions of the pouch. IFX seems to be more efficacious than adalimumab and vedolizumab for CARP. Further prospective, head-to-head evaluations are needed to compare biological therapies in the treatment of CARP and CD of the pouch.

P115 Ustekinumab in DEVELOP: A safety analysis from an Inflammatory Bowel Disease multicenter, prospective, long-term registry of paediatric patients

Abstract Background DEVELOP is a multi-center, global, prospective, observational, longitudinal registry of long-term safety of infliximab (and other treatments) in paediatric patients (pts) with inflammatory bowel disease (IBD) &amp;lt;18 years (yrs) at diagnosis. Over the course of follow-up, many pts required changes in therapy. Ustekinumab (UST) is approved for treatment of Crohn’s disease (CD) in adults and is currently being evaluated for safety/efficacy in paediatric pts. This report focuses on assessment of safety of UST in paediatric pts with CD from DEVELOP. Methods Data included paediatric pts treated with UST from 31 May 2007 through 30 June 2022; data are collected every 6 months. The analyzed population included: all paediatric pts (all pts), pts weighing &amp;lt;40kg (&amp;lt;40kg group), and pts weighing ≥40kg (≥40kg group). Assessments included medical and treatment history, UST exposure, adverse events (AEs), serious AEs (SAEs), CD-related SAEs leading to hospitalization, IBD surgeries, serious and opportunistic infections, malignancies, and deaths. Results A total of 150 pts received UST (49.3% females); 31 in the &amp;lt;40kg group and 119 in the ≥40kg group (Table 1). Most treated pts (92.0%) were 12-17yrs. The majority (91%) of pts were initially dosed with UST every 8 weeks (q8w); at the last known dose, 64% received UST q8w and 22% q4w. Mean (SD) age of initial UST exposure was 15yrs (2.19). Prior IBD surgery was reported in 65.3% pts. The majority of pts (98%) had prior biologic therapy and 72% received ≥2 biologics prior to UST. Overall, 37/150 (24.7%) of pts discontinued UST during follow-up, with a mean (SD) time to discontinuation of 16.7 (17.00) months; 84/150 (56.0%) were exposed to UST for ≥24 months. Rates (events/100 pt-yrs) of AEs were higher in the ≥40kg group (177.62) than in the &amp;lt;40kg group (101.27). Rates of SAEs were slightly lower among the ≥40kg group (25.42) vs &amp;lt;40kg (32.67). There were no SAEs related to infusion or injection site reactions. Rates of serious infections and CD-related hospitalizations were low and similar between groups, and rates of IBD-related surgeries were similar between groups (Figure 1). One malignancy (malignant carcinoid tumor) was reported in a female (18yrs) in the ≥40kg group with a history of prior therapy with vedolizumab, methotrexate, and 6-MP. No deaths or opportunistic infections were reported. Conclusion The safety profile observed for this off-label use of UST in paediatric CD pts in DEVELOP was similar to that of the treated adult population, despite most paediatric pts having prior biologic exposure. No new safety signals are identified in this paediatric population.

P528 Re-induction of intravenous ustekinumab to maintain drug persistence. A UK experience

Abstract Background In this study we seek to add to the body of knowledge on the practical use of ustekinumab in patients with Crohns and Colitis. Patients commencing ustekinumab will mostly have failed, or are intolerant to, conventional biologic agents and therefore have a limited number of medical options available to manage their disease. Results from the IM-UNITI long-term extension study have shown that a proportion of patients will lose response to maintenance dose therapy, and a small number of studies have suggested that repeated induction doses of this therapy can prolong its effective use and allow patients a greater period of disease free remission. Shrewsbury and Telford hospital NHS trust is a multi-site UK hospital serving a large population in the west-midlands region which has established the routine use of usetkinumab therapy over 5 years ago and by reviewing data on our patient cohort we aimed to identify characteristics amongst patients who have required reinduction doses and how effective they have been in maintaining remission. Methods In this retrospective, interventional study two researchers gathered data including baseline characteristics, disease type and distribution, previous surgical and medical therapies and time from diagnosis on all patients who had received ustekinumab therapy over the past five years. We used biochemical and endoscopic data, as well as clinical records, to determine the efficacy of ustekinumab on the disease course. We identified the subgroup of patients requiring reinduction doses and noted whether this was a successful intervention and sought to describe similarities which could help identify patients at risk of failing maintenance therapy in future. Results Data from 213 patients was gathered (Crohns: 150, UC: 61, IBDU: 2) and of which 87 (Crohns: 63, UC: 24) received reinduction doses. Average time to reinduction from therapy commencement was 19.5 months (Crohns) and 16.3 months (UC) respectively. Of the reinduction group 63% showed improvement in their disease control and a variety of characteristics were noted amongst the successful patients for discussion including disease location, presence of perianal disease and time from diagnosis. Conclusion Ustekinumab reinduction is an important area for further research as it allows patients to prolong their successful therapy and delay the need for surgical intervention for difficult to manage disease. This study suggests characteristics which could inform further trials and establish protocols to aid clinicians when making decisions about switching biologic therapies.

P873 Ustekinumab Real World Evidence Study (UndieS): Assessing the suitability of patients treated in routine clinical care for participation in the pivotal phase 3 clinical trial

Abstract Background Phase 3 randomised controlled trials (RCTs) are recognised as the gold standard for measuring the efficacy of new medicines and are essential for licensing new products. To maximise internal validity, RCTs recruit a highly selected, carefully defined group of participants, whereas patients treated in routine practice are much more heterogeneous. We set out to describe the real-world use of ustekinumab and assess the proportion of treated patients who would have been eligible for the relevant registration studies. Methods UndieS is a UK-based, multicentre, prospective, observational study investigating the effectiveness of ustekinumab in 593 Crohn’s disease patients. Objective evidence of active Crohn’s disease (biochemical or endoscopic) and/or failure or intolerance to another therapy were the only entry criteria. Within the limits of the study, we compared participants’ characteristics with the eligibility requirements of the UNITI clinical trial programme. The pragmatic modified Harvey-Bradshaw Index (mHBI), shown to correlate to CDAI score, was used in UndieS. No endoscopic follow up information was collected. Results 82% of patients treated in this real-world study would not have been eligible for participation in the UNITI programme. Eight RCT eligibility criteria would each be expected to exclude at least 10% of the real-world patient population (figure 1). A low disease activity score was the eligibility criterion most frequently expected to render UndieS participants ineligible for the UNITI programme with 61% of predicted CDAI scores (i.e. estimated from mHBI) falling below the threshold for RCT eligibility, despite 80% of those treated having objective evidence of inflammation and 55% failed/ were intolerant to an alternative therapy. Only 13% of participants were using corticosteroids at baseline. 59% of UndieS participants had previously failed or been intolerant to at least one anti-TNFα medication. For those who would have been ineligible for the RCT based on laboratory tests, an elevated ALT was the commonest abnormality among UndieS participants. The requirements for multiple venepunctures and pregnancy avoidance were the most relevant impediments for UndieS patients, with 28% of females of childbearing potential not willing to agree to the specified conditions. Conclusion Within the limitations of this study, we have demonstrated a significant disparity between participants in phase 3 RCTs and patients treated in routine clinical care. This questions the applicability of efficacy studies to real world clinical practice. Data from high quality, observational studies should complement findings from RCTs to support decision makers. Future work will investigate whether outcomes differ according to RCT eligibility.

Controversies in the management of anti-TNF therapy in patients with Crohn’s disease: a Delphi consensus

BackgroundDespite research, there are still controversial areas in the management of Crohn’s disease (CD).ObjectiveTo establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD.MethodsClinical controversies...

Use of real-world data to assess the effectiveness of ustekinumab in treating IBD patients: a retrospective linked database study in northwest London

ABSTRACT Background Data on the optimum positioning of biologics in the treatment of inflammatory bowel disease (IBD) are limited. Research design and methods This was a longitudinal retrospective study of linked health-care data from northwest London, UK, for adults who started ustekinumab for IBD from 1 April 20161 April 2016 to 1 April 20211 April 2021. We compared outcomes by line of therapy (1 vs. 2 or 3+) and age group (18‒59 years or ≥ 60 years). In an analysis of CD patients, we calculated risks of IBD-related hospitalization, IBD-related abdominal surgery, ustekinumab persistence, and switching by line of therapy. Results Of 163 patients screened, 149 were eligible. Age had no effect on outcomes. Elective all-cause hospital admissions were significantly higher when ustekinumab was used as second-line or third-line therapy compared with first-line treatment (p = 0.0048 and p = 0.001, respectively). In CD patients the numbers of hospital admissions were also higher with second-line or third-line therapy (p = 0.040 and p = 0.018, respectively). Use of ustekinumab as third-line therapy significantly increased the risk of IBD-related hospitalization (hazard ratio 2.5, 95% CI 1.1‒5.6, p = 0.029), IBD-related abdominal surgery (9.45, 1.2‒75.7, p = 0.03), and switching (14.6, 1.6‒131.0, p = 0.02). Drug persistence risks did not differ. Conclusions These findings support the use of ustekinumab as first-line therapy.

Ustekinumab as induction and maintenance therapy for ulcerative colitis – national extended follow-up and a review of the literature

ABSTRACT Introduction Ustekinumab use in ulcerative colitis had shown low adverse event and high persistence rates to 3 years via the UNIFI long-term extension study. Outcomes beyond 3 years have not been previously described. We describe the safety signals of the entire UNIFI Australian population beyond 3 years. Methods This retrospective multicenter observational cohort study recruited from all Australian UNIFI centers. The primary outcome was safety via adverse events. Secondary outcomes included the clinical relapse rate on ustekinumab, and the need to switch from ustekinumab to an alternate agent. Results There were 14 patients [11 male, mean age 47 (±14) years], with a median diagnosis of 10.8 (±4.5) years prior to UNIFI enrollment. Median follow-up was 298 weeks (5.7 years) (Interquartile range (IQR): 220–311 weeks). Within the long-term extension, there were three serious adverse events and one minor event. 42.9% (6/14) patients had clinical relapses, of which clinical remission was recaptured in 83.3% (5/6). 85.7% (12/14) persisted on ustekinumab in the long-term, with 7.1% (1/14) electively ceasing ustekinumab and 7.1% (1/14) changed from ustekinumab due to clinical relapse. Conclusion For moderate-to-severe UC in Australia, ustekinumab maintained efficacy beyond 3 years with a high persistence rate and no new safety signals. Trial Registration The trial is registered at ANZCTR (identifier: ACTRN12622001332718).

IL12/23 Blockade with Ustekinumab as a Treatment for Immune-Related Cutaneous Adverse Events.

Background: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is reminiscent of the psoriasiform/lichenoid ircAE phenotype. We report the use of ustekinumab as a therapeutic option. Methods: Patients at Memorial Sloan Kettering Cancer Center, New York, who received immune checkpoint inhibitors and were treated with ustekinumab or had the keywords "ustekinumab" or "Stelara" in their clinical notes between 1 March 2017 and 1 December 2022 were retrospectively identified via a database query. Documentation from initial and follow-up visits was manually reviewed, and response to ustekinumab was categorized into complete cutaneous response (CcR, decrease to CTCAE grade 0), partial cutaneous response (PcR, any decrease in CTCAE grade exclusive of decrease to grade 0), and no cutaneous response (NcR, no change in CTCAE grade or worsening). Labs including complete blood count (CBC), cytokine panels, and IgE were obtained in a subset of patients as standard of care. Skin biopsies were reviewed by a dermatopathologist. Results: Fourteen patients with psoriasiform (85.7%), maculopapular (7.1%), and pyoderma gangrenosum (7.1%) ircAEs were identified. Ten (71.4%) receiving ustekinumab had a positive response to treatment. Among these 10 responders, 4 (40%) demonstrated partial cutaneous response and 6 (60%) demonstrated complete cutaneous resolution. Six patients (42.9%) experienced interruptions to their checkpoint inhibitor treatment as a result of intolerable ircAEs, and following ircAE management with ustekinumab, two (33.3%) were successfully rechallenged with their checkpoint inhibitors. On histopathology, patients primarily had findings of interface or psoriasiform dermatitis. No patients reported an adverse event related to ustekinumab. Conclusions: Ustekinumab showed a benefit in a subset of patients with psoriasiform/lichenoid ircAEs. No safety signals were identified. However, further prospective randomized controlled trials are needed to confirm our findings.

Use of ustekinumab after other biological therapies in moderate-severe psoriasis: Real long-term data

ObjectiveUstekinumab is used in moderate-severe plaque psoriasis with inadequate response to anti-tumour necrosis factor a drugs. Recent studies support the need to assess real long-term data. The aim of this study was to evaluate the real long-term effectiveness and safety of ustekinumab in moderate-severe plaque psoriasis refractory to 2 anti-tumour necrosis factor a drugs. MethodRetrospective descriptive study from January 2010 to March 2019. The study included patients with moderate-severe plaque psoriasis previously treated with at least 2 anti-tumour necrosis factor a biologic drugs. The effectiveness endpoints were Psoriasis Area and Severity Index 90 and 75 response rates at weeks 24, 48, 72, and 96. Safety was assessed using adverse effects and treatment withdrawal. ResultsA total of 36 patients were included (men, 61%). Ustekinumab was used after treatment with 2 anti-tumour necrosis factor a drugs in 88.9% of patients. The biologic drugs most frequently administered prior to ustekinumab were infliximab (94.4%) and etanercept (91.7%). It was observed that at least 66.7% of patients reached Psoriasis Area and Severity Index 90 at weeks 24, 48, 72, and 96. Adverse effects were recorded in 6 patients. There were no treatment withdrawals. ConclusionsUstekinumab showed real long-term effectiveness and safety in moderate-severe plaque psoriasis with inadequate response to 2 previous anti-tumour necrosis factor a drugs.

Comprehensive Review of Ustekinumab Utilization in Inflammatory Bowel Diseases: Insights from the ClinicalTrials.gov Registry.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic inflammatory conditions affecting the gastrointestinal tract. To achieve and sustain remission, effective treatment strategies are necessary. Ustekinumab, a biologic agent targeting interleukin-12 and interleukin-23, has emerged as a significant therapeutic option for moderate to severe IBD. To gain insights into the utilization of Ustekinumab for IBD, we conducted a comprehensive review of the ClinicalTrials.gov registry. A comprehensive search of the ClinicalTrials.gov was conducted to find all clinical trials involving the use of Ustekinumab in IBD patients. As of December 30th, 2022, 69 clinical trials were identified that included IBD and Ustekinumab. The study list was saved, and those clinical trials that fitted the definition of targeted therapy were included in the review. The results showed that Ustekinumab was associated with significant improvements in the clinical response and remission rates, in both Crohn's disease and ulcerative colitis patients. Additionally, the safety profile of Ustekinumab was generally favourable, with low rates of adverse events reported. In terms of study design, most of the relevant studies found in the database were interventional studies. The investigation focused on completed studies and found that there were a limited number of clinical trials with interventional measures. Ustekinumab appears to be a promising treatment option for patients with IBD, with the potential to provide significant clinical benefits and a favourable safety profile. Further research is warranted to confirm these findings and explore optimal dosing and treatment regimens.

Variation in access and prescription of vedolizumab and ustekinumab in paediatric patients with inflammatory bowel disease: a UK-wide study

BackgroundTherapeutic options for paediatric inflammatory bowel disease (IBD) are limited, especially for younger children. Unlike in adults, vedolizumab and ustekinumab are not licensed for paediatric use in the UK. We...

Rates and Predictors of Long-term Clinical Outcomes in Patients With Perianal Crohn's Disease on Biologic Therapy.

Perianal Crohn's disease (pCD) represents an aggressive phenotype with limited studies on long-term outcomes. We evaluated 5-year outcomes of these patients on biologic therapies. We performed a retrospective analysis of patients with pCD at a tertiary medical center. We used Kaplan-Meier curves to estimate rates and multivariate logistic regression to identify predictors of long-term outcomes. We included 311 patients with pCD of which 168 patients were started on biologics [138 anti-tumor necrosis factor (TNF) α, 14 vedolizumab, 16 ustekinumab] at the time of diagnosis. Anti-TNF use at the time of diagnosis was associated with decreased rates of perianal abscess recurrence [hazard ratio (HR)=0.48, 95% confidence interval (CI): 0.32-0.74], whereas ustekinumab use was associated with increased rates of perianal fistula closure (HR=3.58, 95% CI: 1.04-12.35) and decreased rates of perianal abscess recurrence (HR=0.20, 95% CI: 0.07-0.56) at follow-up. Among patients who failed their first anti-TNF, switching to another anti-TNF was associated with decreased rates of colectomy (HR=0.20, 95% CI: 0.04-0.90) and permanent diversion (HR=0.16, 95% CI: 0.03-0.94) compared with ustekinumab, whereas vedolizumab use was associated with decreased perianal fistula closure (HR=0.22, 95% CI: 0.05-0.96) compared with ustekinumab. Predictors of colectomy included colonic disease (odds ratio=2.71, 95% CI: 1.36-5.38) and anal stenosis (odds ratio=4.44, 95% CI: 1.59-12.43). Type of biologic use at the time of pCD diagnosis or after first anti-TNF failure may be associated with long-term outcomes in patients with pCD.

Ustekinumab in the treatment of acute disseminated pyoderma gangrenosum in a patient with Crohn's disease.

Pyoderma gangrenosum (PG) is an auto-inflammatory dermatosis characterized by lesions that often cause ulcers. We present a case of successful ustekinumab treatment for acute general PG in a 31-year-old woman with coexisting Crohn's disease (CD). For a month, the patient suffered from skin ulcers, two of them deep and necrotic; a histopathological examination revealed PG. Treatment included: methylprednisolone, azathioprine, betamethasone, gentamicin and zincic ointments, antiseptic compresses, and adalimumab therapy. Due to resistance to the implemented treatment, the patient was enrolled in a clinical trial that included the administration of an anti-cytokines drug, ustekinumab. Subsequently, a significant reduction was observed in the severity of symptoms of PG with no relapse. The use of ustekinumab in patients with PG who have an inadequate response to current treatment or cannot receive first-line treatment can be considered. This applies especially to patients with accompanying autoimmune diseases such as CD.