Article Topic: Positioning Ulcerative Colitis Therapies in 2022 and Beyond.

PURPOSE OF REVIEW: Ulcerative colitis (UC) is a chronic disease with an increasing incidence. Recent guidelines emphasize treating toward objective targets, requiring the use of effective, steroid-sparing therapies. This review summarizes the safety and efficacy data of available therapies as well comparative effectiveness studies in order to help the reader make rational treatment decisions. RECENT FINDINGS: Following the approval of tumor necrosis factor alpha antagonists, we have seen recent regulatory approval of several additional biologic and small molecule agents from several therapeutic classes (integrin antagonists, interleukin 12/23 antagonists, Janus kinase inhibitors, and sphingosine-1-phosphate receptor antagonists) for UC. Randomized, controlled trials, real-world analyses, and network meta-analyses have investigated the comparative safety and efficacy of these therapies in order to help clinicians better position these therapies in clinical practice. Numerous agents are now approved for the treatment of UC. This evidence-based review will help the reader understand the important factors weighing into treatment decisions for patients with UC and enable patient education and discussion with a focus on a shared decision-making approach.

Identification of the Most Effective Position for Ustekinumab in Treatment Algorithms for Crohn's Disease.

BACKGROUND & AIMS: Ustekinumab is a monoclonal antibody against interleukin 12 and interleukin 23 that has been approved by the Food and Drug Administration for treatment of Crohn's disease (CD). We sought to identify the ideal position for ustekinumab in treatment algorithms for CD. METHODS: We constructed a Markov model to identify an optimal treatment sequence for CD that included ustekinumab for 1 year or more. The base case was a 35-year old male with moderate to severe CD who had not previously received biologic or immunomodulator therapy. The standard of care treatment algorithm was defined as initial therapy with infliximab and azathioprine, followed by adalimumab and azathioprine, vedolizumab, and lastly surgical resection. The model assessed positions for ustekinumab before standard of care, ustekinumab after infliximab and azathioprine but before the remaining treatments, after infliximab, azathioprine, and adalimumab but before vedolizumab and surgery, or after the other biologics but before surgery. We derived transition probabilities and quality adjusted life years (QALYs) from relevant trials, observational studies, and time trade-off analyses. Primary analyses consisted of first order Monte Carlo simulation of 100 trials of cohorts of 100,000 individuals. RESULTS: Ustekinumab as first-line therapy yielded the greatest QALYs (incremental effectiveness, 0.016-0.020 QALYs), resulting in 10% more patients in remission or response, and 2% fewer surgeries at 1 year, compared with other algorithms. The model was not sensitive to 25% variation in transition probabilities. CONCLUSIONS: In a simulation based on a 35-year old male patient with moderate to severe CD, we found that ustekinumab as the first-line biologic therapy yields greater QALYs at the end of 1 year than compared with use later in the CD treatment algorithm.

Transplant related ocular surface disorders: Advanced techniques for ocular surface rehabilitation after ocular complications secondary to hematopoietic stem cell transplantation.

HSCT has been linked to the development of an assortment of ocular surface complications with the potential to lead to permanent visual impairment if left untreated or if not treated early in the course of disease. Strategies for therapy include maintenance of lubrication and tear preservation, prevention of evaporation, decreasing inflammation, and providing epithelial support. The ultimate aim of treatment is to prevent permanent ocular sequelae through prompt ophthalmology consultation and the use of advanced techniques for ocular surface rehabilitation. We describe several rehabilitation options of ocular surface complications occurring secondarily during the post-HSCT course.

A case report of primary cutaneous marginal zone lymphoma treated with intralesional steroids.

IMPORTANCE: Primary cutaneous marginal zone lymphoma (PCMZL) is a low-grade malignant B-cell lymphoma that appears in the skin without any extracutaneous manifestations. Therapeutic mainstays for PCMZL have primarily included radiotherapy and surgery. Intralesional steroids have been found to resolve the lesions caused by PCMZL, but there is a dearth of literature regarding this therapy indicating that this is not a commonly favored treatment option. OBSERVATIONS: We present a case of 60-year-old woman who presented with PCMZL on her right eyebrow. Three years later, after two courses of radiation and one relapse, the patient presented with new lesions on both arms, consistent once again with PCMZL. At this time, therapy with nine rounds of intralesional triamcinolone was attempted. After each round of triamcinolone, gradual improvement of the lesions was noted until complete resolution occurred. CONCLUSIONS AND RELEVANCE: This case reminds practitioners that intralesional corticosteroids can be effectively and safely used to treat localized PCMZL. Intralesional steroids are less invasive, cheaper, and easier to administer than the majority of other recommended therapies for PCMZL. Thus, although they are often overlooked, intralesional corticosteroids should be more often considered when developing a treatment plan for localized PCMZL.

A case report of primary cutaneous histoplasmosis requiring deep tissue sampling for diagnosis.

IMPORTANCE: This is a case of primary cutaneous histoplasmosis, without any systemic involvement, that occurred without a history of trauma. Due to its rarity and varied clinical presentation, there is much difficulty in diagnosis of this disease entitiy, especially in differentiating it from pyoderma gangreosum. This patient required deep tissue sampling and a DNA probe for Histoplasma to establish a time-sensitive diagnosis as multiple superficial biopsies are nondiagnositic.

An Unusual Hiccup: Severe Singultus as a Symptom in Ulcerative Colitis.

Inflammatory bowel disease encompasses a group of chronic inflammatory conditions associated with both intestinal and extraintestinal manifestations. We present a 26-year-old man with a history of ulcerative colitis who presented with a disease exacerbation associated with severe intractable hiccups. We report a unique clinical symptom associated with severe ulcerative colitis and the diagnostic dilemma associated with this presentation. This case highlights the importance of recognizing unusual symptoms that can be associated with inflammatory bowel disease exacerbations and demonstrates the therapeutic potential of effective therapy of the underlying inflammatory disease.

Temporal Trends in Perceptions of Anti-tumor Necrosis Factor Risks and Benefits in an Online Community of Patients With Crohn's Disease.

Background and Aims: Anti-tumor necrosis factor agents (anti-TNFs) have become one of the primary medical therapies for Crohn's disease (CD). We analyzed perceptions of infliximab and adalimumab in a large online community to better understand the information patients receive. Methods: Reddit, a vast online community, has several inflammatory bowel disease communities, the largest being /r/CrohnsDisease (rCD), with over 41,000 members. To better understand patient perceptions of biologics, we searched rCD for posts related to "infliximab," "adalimumab," and their relevant trade names. The top 20 yearly posts were extracted from 2011 to 2015 and 2011 to 2017, respectively. Manifest coding was performed. Codes were reassessed every 20 posts, resulting in 6 main sentiments. Total codes and per-comment codes were calculated for each sentiment. Percentages for each category were calculated by dividing by the total number of coded sentiments that year. Trends in rates of each sentiment were assessed using Spearman's correlation coefficients. Results: 4486 comments were analyzed, and 4684 sentiments met our criteria. Negative sentiments decreased for both anti-TNFs over time (infliximab: rho = -0.90, P = .04, adalimumab: rho = -0.79, P = .04). In our primary analysis, adalimumab injection-related posts increased from 2012 to 2017 (rho = 0.83, P = .04). Positive sentiments and sentiments regarding drug costs, loss of efficacy, and diet remained stable. For infliximab and adalimumab, comment volume increased significantly over time (rho 0.90; P = .04, rho 0.89, P = .01). Conclusion: Our analysis of a large online community suggests a growing acceptance of biologic therapies among patients with CD over time. These data provide additional insight into the multifaceted framework shaping patients' perceptions of anti-TNFs.

Gastrointestinal and Hepatic Disease in the Inflammatory Myopathies.

Although muscle weakness is the pathognomonic feature of idiopathic inflammatory myopathies, systemic organ involvement is not uncommon. The gastrointestinal and hepatic manifestations are well known. Oropharyngeal dysphagia is the most common gastrointestinal symptom and can be severe. Gastric and small intestinal motility disorders, including chronic intestinal pseudo-obstruction, celiac disease, and inflammatory bowel disease have been described. Comprehensive cancer screening is warranted soon after the diagnosis of inflammatory myopathies due to high risk of occult malignancies. Elevated aminotransferases may suggest muscular injury rather than hepatic dysfunction. Knowledge regarding systemic involvement of inflammatory myopathies can assist in timely diagnosis of these complex disorders.