Ustekinumab is a first-line drug for Crohn\'s disease. However, little is known about its potential adverse effects on renal function. We present the case of a 42-year-old man with Crohn\'s disease who developed chronic renal dysfunction during ustekinumab treatment, which resolved after discontinuing ustekinumab. The findings underscore the importance of close monitoring of renal function in patients receiving ustekinumab, particularly those with preexisting kidney disease or risk factors for renal dysfunction.

Vitiligo is a chronic depigmenting disorder that significantly impacts the quality of life of patients. Though there have been significant advancements in targeted therapies in skin diseases such as psoriasis or eczema, the progress in the treatment of vitiligo has been slow, with minimal studies assessing the effect of biologics, though there has been recent evidence of the effectiveness of JAK inhibition. This paper reviews the published case reports and studies for the use of systemic targeted therapies including biologics and JAK inhibitors in vitiligo.

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BACKGROUND: Hidradenitis suppurativa (HS) is a frequently debilitating, inflammatory skin condition. Patients may have a limited response to adalimumab, currently the only Food and Drug Administration (FDA)-approved biologic treatment for HS. Ustekinumab is an interleukin-12/23 inhibitor that has been utilized in HS, but there is a lack of an updated systematic review on its efficacy and safety. The aim of this study is to perform a systematic review and meta-analysis of the literature on the efficacy and safety of ustekinumab for HS.
METHODS: In October 2022, MEDLINE and Embase databases were searched for articles on ustekinumab in HS. Data extraction was performed on relevant articles by two reviewers. The primary study outcome was the pooled response rate of HS to ustekinumab. A fixed-effects meta-analysis was performed, and Cochran\'s Q statistic and I squared index were used to assess heterogeneity. Statistical significance was determined at p < 0.05. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
RESULTS: From 2012 to 2022, ten articles (nine case series and one prospective trial) with 88 patients met the inclusion criteria. Patients with reported disease severity had Hurley stage II (17.6%, 12/68) or III (82.4%, 56/68) disease. The majority (80.7%, 71/88) had previously failed at least one biologic treatment. A meta-analysis of all ten studies showed a pooled response rate of 67% (95% CI 0.57-0.76). Study limitations include a small number of patients and randomized controlled trials (RCTs).
CONCLUSIONS: Ustekinumab may be a helpful treatment option to consider for HS that is recalcitrant to first-line biologic therapies, but RCTs are needed to determine optimal dosing regimens and the specific patient populations that would benefit the most from this agent.

BACKGROUND: Metastatic Crohn\'s disease is a rare disorder characterized by various granulomatous skin lesions that occur independently of gastrointestinal tract involvement. However, currently there is no standardized care or specific treatment. Therapeutic approaches include immunosuppressive agents, such as corticosteroids, azathioprine, and monoclonal antibodies targeting inflammatory cytokines like tumor necrosis factor (TNF).
METHODS: We present a case of a 29-year-old western European woman with significant blind ending abdominal subcutaneous fistulas and abscesses, who sought evaluation in the dermatology department. Histological examination revealed multiple epithelioid cell granulomas. There was no evidence of infectious or rheumatologic diseases such as sarcoidosis. The tentative diagnosis was metastatic Crohn\'s disease, which was not related to an intestinal manifestation of the disease. The patient responded to infliximab but had to discontinue it due to an allergic reaction. Subsequent adalimumab treatment failed to induce clinical remission; thus, therapy was switched to ustekinumab, resulting in a positive response. Written informed consent for publication of their clinical details and clinical images was obtained from the patient. For our study more than 1600 publications were screened for cases of metastatic Crohn\'s disease on PubMed database. 59 case reports with 171 patients were included in the analysis and evaluated for localization, diagnostic and therapeutic approaches, and complications and were summarized in this review.
CONCLUSIONS: The successful ustekinumab treatment of a patient with metastatic Crohn\'s disease underscores the potential of this minimally investigated therapeutic option, highlighting the need for future treatment guidelines given the increasing prevalence of such cases.

Background: Anti-tumour necrosis factor (TNF) agents are effective in Crohn\'s disease (CD), but some patients lose responsiveness and require alternative biologic therapy. Until recently, ustekinumab and vedolizumab were the only other biological agents approved for use in CD. There are no randomised trials which compare the efficacy of these two agents in patients with anti-TNF refractory disease, but several retrospective cohort studies have compared their effectiveness in this setting. Aim: To review the effectiveness of ustekinumab and vedolizumab in anti-TNF refractory patients with CD. Methods: We included studies that compared the effectiveness of ustekinumab and vedolizumab in treating patients with anti-TNF refractory CD. We recorded the sample size, primary and secondary outcome measures and whether the studies employed adjustments for appropriate confounders. Results: Fourteen studies were included with a total sample size of 5651, of whom 2181 (38.6%) were treated with vedolizumab and the rest were treated with ustekinumab (61.4%). Of the fourteen studies included, eight found ustekinumab to be more effective in achieving clinical remission/steroid-free remission in the induction phase or during maintenance therapy (at least 1-year post-treatment) or that treatment persistence rates with ustekinumab were higher than with vedolizumab. Only one study reported vedolizumab to be superior during the maintenance phase in terms of clinical remission or treatment persistence rates. Biochemical outcomes were reported in five studies, two of which showed superiority for ustekinumab at 14 weeks and the other at 52 weeks. Only two studies reported endoscopic and/or radiologic outcomes; of these, one study showed ustekinumab to be significantly better at achieving endoscopic and radiologic responses. Adverse outcomes were broadly comparable, barring a single study which reported a lower hospitalisation rate for severe infection with ustekinumab. Conclusions: Most studies found ustekinumab to be more effective or non-inferior to vedolizumab in treating patients with anti-TNF refractory CD. Although many studies adjusted appropriately for confounders, the possibility of residual confounding remains and further data from prospective studies are warranted to confirm these findings. Further studies are required to compare these two therapies to other emerging therapies, such as Janus-kinase inhibitors.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract usually characterized by diarrhea, rectal bleeding, and abdominal pain. IBD includes Crohn\'s disease and ulcerative colitis as the main entities. IBD is a debilitating condition that can lead to life-threatening complications, involving possible malignancy and surgery. The available therapies aim to achieve long-term remission and prevent disease progression. Biologics are bioengineered therapeutic drugs that mainly target proteins. Although they have revolutionized the treatment of IBD, their potential therapeutic benefits are limited due to large interindividual variability in clinical response in terms of efficacy and toxicity, resulting in high rates of long-term therapeutic failure. It is therefore important to find biomarkers that provide tailor-made treatment strategies that allow for patient stratification to maximize treatment benefits and minimize adverse events. Pharmacogenetics has the potential to optimize biologics selection in IBD by identifying genetic variants, specifically single nucleotide polymorphisms (SNPs), which are the underlying factors associated with an individual\'s drug response. This review analyzes the current knowledge of genetic variants associated with biological agent response (infliximab, adalimumab, ustekinumab, and vedolizumab) in IBD. An online literature search in various databases was conducted. After applying the inclusion and exclusion criteria, 28 reports from the 1685 results were employed for the review. The most significant SNPs potentially useful as predictive biomarkers of treatment response are linked to immunity, cytokine production, and immunorecognition.

UNASSIGNED: To describe the published efficacy and adverse event rates associated with existing biologics for the treatment of pityriasis rubra pilaris (PRP).
UNASSIGNED: A literature review using the PubMed database (January 1990-July 2023) was conducted. Multiple search combinations were conducted using \"pityriasis rubra pilaris\" and various biologics as keywords to identify relevant articles.
UNASSIGNED: Inclusion criteria included all study types that were published within the past 30 years in English and mentioned at least one biologic and PRP. A preliminary search yielded a total of 499 results. After screening using inclusion and exclusion criteria, 77 relevant articles (69 case reports, 5 case series, 2 clinical trials, and 1 retrospective analysis) were analyzed.
UNASSIGNED: TNF-α inhibitors have been evaluated and are effective in treating PRP. However, recent treatment with anti-interleukin (IL)-17 and anti-IL-23 therapies such as ustekinumab, secukinumab, and ixekizumab are emerging as new treatment options with a mean improvement in PRP Area and Severity Index scores, change in severity of erythema, scaling, and thickness of PRP lesions. From initial clinical trials, secukinumab and ixekizumab are promising treatment options for achieving remission.
UNASSIGNED: This review compares the efficacy for numerous biologics and a discussion to guide clinicians on benefits and risks in choosing a biologic for PRP patients.
UNASSIGNED: Biologics may be a favourable treatment option leading to greater patient adherence due to reduced dosing frequencies, improvement in quality of life, and reduction in frequency and severity of flares.

Ustekinumab is a monoclonal antibody targeting the p40 subunit of IL-12 and IL-23, approved for treating psoriasis, psoriatic arthritis, and inflammatory bowel disease. Despite a remarkable success in treating chronic inflammatory conditions and a generally favorable safety profile, its role in inducing rare adverse events, such as interstitial pneumonia and acute respiratory distress syndrome (ARDS), remains largely uncharted. We report a case of a 66-year-old male patient treated with Ustekinumab for severe psoriasis who, after almost two years of treatment, developed dyspnea, asthenia, and fever progressing to non-infectious pneumonia and ARDS leading to ICU admission. Moreover, we conducted a literature review on Ustekinumab-associated pulmonary complications. Our case underscores the importance of appropriate and long-term clinical monitoring in patients on Ustekinumab treatment, particularly considering the potential lung complications. The possibility of non-infectious pneumonitis should be considered alongside infectious causes, facilitating prompt management in the case of negative infectious screening. Additionally, the severity of ARDS underscores the importance of timely recognition and proper management. Further investigations are recommended to investigate the immunological basis of Ustekinumab-induced ARDS for designing appropriate monitoring strategies.

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.