A practical guide to selecting and using new ulcerative colitis therapies.

PURPOSE OF REVIEW: Several new biologics (mirizikizumab) and small molecules (upadacitinib, ozanimod, etrasimod) are approved for the treatment of moderate-to-severe ulcerative colitis. To date, there are no head-to-head trials to guide positioning and use of these newer agents. RECENT FINDINGS: From phase III clinical trials, in the biologic experienced patient, induction with ozanimod, etrasimod, and mirizikizumab had lower clinical remission rates, whereas upadacitinib's clinical remission rates remained similar. Indirect evidence using network meta-analysis suggests upadacitinib may be more efficacious than other advanced therapies for the treatment of ulcerative colitis in both the bio-naive and experienced patient. Upadacitinib was found to have the highest risk for adverse events. SUMMARY: These newer agents add novel mechanisms of action to the expanding therapeutic armamentarium of advanced therapies to treat ulcerative colitis. Based on expert opinion and available data to date, we propose a practical guide on positioning of these new agents for the treatment of ulcerative colitis. In mild-to-moderate disease, one should consider using ozanimod or etrasimod as first-line agents. In moderate-to-severe disease, we favor using mirizikizumab as first-line agent. In patients who have failed an anti-tumor necrosis factor agent, upadacitinib or mirizikizumab should be considered using patient factors and safety to guide one's decision between these two agents.

Indications and safety of newer IBD treatments in the older patient.

PURPOSE OF REVIEW: Treatment of inflammatory bowel disease (IBD) in the elderly requires special attention to treatment efficacy while considering drug safety, other medical comorbidities, and the patients' risk for treatment related adverse events. In this article, we reviewed the indications and safety of the newer IBD therapies in the older IBD patient beyond anti-TNF agents, thiopurines, and corticosteroids. RECENT FINDINGS: Vedolizumab, ustekinumab, and risankizumab have favorable side effect profiles with regards to infections and malignancy. Ozanimod has a favorable side effect profile with regards to infection and malignancy, however cardiac events and macular edema are potential risks. Tofacitinib and upadacitinib are associated with an increased risk of serious infections, herpes zoster, malignancy, and have potential for an increased risk of cardiac events and thrombosis. From a safety profile perspective, vedolizumab, ustekinumab, and risankizumab should be considered first line treatment options for moderate-to-severe IBD in the elderly. Risk-benefit discussions are indicated for ozanimod, tofacitinib, and upadacitinib.

A Novel Remote Patient and Medication Monitoring Solution to Improve Adherence and Persistence With Inflammatory Bowel Disease Therapy (ASSIST Study): Protocol for a Randomized Controlled Trial.

BACKGROUND: Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions of the gastrointestinal tract. Although adherence to IBD therapies is associated with improved clinical outcomes, overall adherence is poor. Consequently, there is a critical need to develop interventions that monitor adherence in real time and identify reasons for nonadherence to support clinical teams in initiating effective interventions. Recently, electronic- and web-based platforms have been developed to monitor adherence and guide interventions. A novel remote therapy monitoring (RTM) technology, the Tappt digital health system, has been developed to monitor real-time medication adherence patterns through smart label technologies, capture patient-reported outcomes and barriers to care, and process patient data through algorithms that trigger personalized digital and human touch points between clinical visits. Such a digital health solution enables care teams to proactively identify and mitigate nonadherence and worsening clinical outcomes. OBJECTIVE: We propose a 12-month multicenter randomized controlled trial to assess the effectiveness of the Tappt digital health system on adherence, clinical outcomes, and health care use among patients diagnosed with IBD starting a new oral or subcutaneous therapy. METHODS: The digital health system intervention will provide automatic measurement of medication adherence via smart labels for pill bottles or injectors as well as a monitoring platform for providers. The system will prompt patients to complete a two-item assessment of symptoms monthly using the PRO-2 scales for UC and Crohn disease, from which increased symptoms will be alerted to providers. Participants will be randomized 2:1 to the intervention group or the control group, which will receive standard of care. All participants are required to complete questionnaires at baseline as well as at 12, 26, and 52 weeks. Assuming an adherence rate of 0.65 and 0.9 among control and intervention participants, respectively, we will need to enroll 123 participants: 82 (66.7%) in the intervention group and 41 (33.3%) controls. We will compare adherence as measured by the medication possession ratio, defined as the number of days of supply of medication obtained during the observation period out of the total number of days in the observation period, in participants using the RTM versus those receiving standard of care. We will also compare clinical outcomes and health care use in participants using the RTM versus those receiving standard of care. RESULTS: We anticipate starting recruitment in December 2022. CONCLUSIONS: Effective medication adherence monitoring and intervention programs need to be cost-efficient, pose little or no burden to the patient, record reliable data in real time, and provide actionable insights to the health care team. We anticipate the Tappt digital health system to improve the medication possession ratio, clinical outcomes, and health care use compared with standard of care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05316584; https://clinicaltrials.gov/ct2/show/NCT05316584. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/40382.

Safety of anti-TNF agents in pregnancy.

Inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis are associated with adverse pregnancy outcomes. Active maternal disease during pregnancy is associated with additional negative outcomes. Anti-TNF agents are effective treatments for inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. These agents cross the placenta starting in the second trimester, with levels detected for several months after birth. This has led to safety concerns, with continued therapy during pregnancy for both the mother and the infant. This review covers retrospective and prospective data published from various cohorts of pregnant women exposed to anti-TNF agents during pregnancy. It highlights the safety of anti-TNF drugs in pregnancy, breast-feeding, and during the first year of life of the infant.

Patients Perception of Risks and Benefits of Biologic Therapy.

Biologic therapy continues to be underutilized despite its efficacy and overall favorable side effect profile when compared with corticosteroids. Siegel et al found in a well-done, cross-sectional study that patients perceived that corticosteroids were more beneficial, more familiar, and less dreadful than biologics despite perceiving that corticosteroids are more risky. They also found that perception of risk may be influenced by a patient's personality trait. Patients who believe that their health is influenced by their own choices or behaviors perceived biologic therapy less scary compared with patients who believed their health is influenced by chance. Physicians and patients disagree about how much medication-related risk is tolerable for improvements on efficacy. However, they are both willing to accept risks for therapies that offer significant therapeutic benefit. Physicians are tasked to translate complex evidenced-based data accurately and should take into account a patient's personality trait in order to provide individualized care and help guide shared decision-making. Future research should assess physician's personality traits, treatment experiences, and perception of risks, benefits, and dread of IBD medications and how it influences shared-decision making.

Women's Health in Inflammatory Bowel Disease.

About half of all inflammatory bowel disease (IBD) patients are women. It is important that physicians are aware of gender-specific needs women with IBD may have. This review covers general and specific women's health issues related to their IBD. It is intended to be practical and give a brief overview of topics including body image, menstruation, contraception, cervical cancer screening, preconception counseling, anxiety, depression, pregnancy, breastfeeding, menopause, skin exams, vaccines, laboratory monitoring and bone health.

Crohn's Disease of the Esophagus: Clinical Features and Treatment Outcomes in the Biologic Era.

BACKGROUND: Esophageal Crohn's disease (CD) is challenging and often a disabling phenotype of disease. We aimed to report the clinical, endoscopic, histologic features, and treatment outcomes of esophageal patients with CD. METHODS: Esophageal patients with CD evaluated at the Mayo Clinic in Rochester, MN, between January, 1998, and December, 2012, were identified. RESULTS: Twenty-four cases of esophageal CD were identified. The median age of diagnosis was 23 years (range, 12-60). Twenty-one patients (88%) had extraesophageal CD and 8 patients (33%) had oral ulcers at the time of esophageal CD symptom onset. The majority of patients had esophageal-specific symptoms. Mid (29%) or distal (29%) esophagus was the most common site of involvement. Inflammatory esophageal CD (75%) was marked by superficial ulcerations (58%), erythema and/or erosions (50%), deep ulcerations (13%), and pseudopolyps (4%) on endoscopy. Four patients (17%) were found to have esophageal strictures and 2 patients (8%) had fistulizing disease. Chronic inflammation (83%) was seen on biopsy in the majority of cases with 5 patients having associated granulomas. In our series, inflammatory esophageal CD responded to prednisone, topical budesonide, or biologics. Stricturing esophageal CD was successfully treated with a combination of biologic therapy, immunomodulators, and serial dilations with/without steroid injections. Aggressive medical therapy with biologics and endoscopic therapy was used for fistulizing esophageal CD, however, was not universally effective. CONCLUSIONS: Esophageal CD should be considered in all patients with CD with upper gastrointestinal symptoms. Early recognition, diagnosis, and aggressive medical and/or endoscopic treatment are needed for successful outcomes.

Ipilimumab-induced colitis in patients with metastatic melanoma.

Ipilimumab is used for the treatment of metastatic melanoma and is associated with serious immune-related colitis. We aimed to report the clinical features, treatment, and outcomes of patients with ipilimumab-induced colitis. In this retrospective observational study, we identified patients with unresectable melanoma treated with ipilimumab between March 2011 and September 2013. Diarrhea was assessed using the Common Terminology Criteria for Adverse Events, v3.0. Colitis was defined by diarrhea (grade≥2) requiring steroids with or without endoscopic/histologic/radiologic evidence of colitis. A total of 103 patients with metastatic melanoma treated with ipilimumab were identified. Of these, 30 patients (29%) developed diarrhea (all grades), and 23 patients (22%) developed colitis requiring systemic corticosteroid therapy. The median number of ipilimumab doses before onset of diarrhea was 2 (range, 1-4). Six of 23 patients responded to less than 1 mg/kg daily prednisone alone. Fifteen patients required high-dose oral and/or intravenous prednisone (1-2 mg/kg body weight). Six patients had diarrhea refractory to prednisone; five required rescue therapy with budesonide (9-12 mg daily) and one was treated with infliximab (5 mg/kg, three doses). There was one case of severe diarrhea (grade 3) treated successfully with high-dose budesonide (12 mg) monotherapy. Ipilimumab-induced colitis requires early and aggressive medical therapy. Most patients can be successfully managed with systemic corticosteroids. High-dose budesonide is an attractive steroid-sparing agent, however further studies of its efficacy in this setting are needed. Infliximab should be used in refractory cases to avoid colectomy.

Inflammatory bowel disease in women of reproductive age.

Management of inflammatory bowel disease in women of reproductive age requires special attention. Even though fertility in women without previous pelvis surgery is similar to the general population, active disease at conception and during pregnancy can lead to unfavorable pregnancy and fetal outcomes. In general, most medications needed to treat inflammatory bowel disease are low risk during pregnancy and breastfeeding. Achieving and maintaining disease remission, patient education, and a multidisciplinary team approach is the key to a successful pregnancy.