Mirikizumab: A New Therapeutic Option for the Treatment of Ulcerative Colitis.

OBJECTIVE: To review the pharmacologic and clinical profile of mirikizumab in the treatment of moderate to severe ulcerative colitis (UC). DATA SOURCES: A PubMed search was performed from inception to December 2023 using keywords mirikizumab, interleukin-23 inhibitor, and UC. Information was also obtained from package inserts as well as published abstracts. STUDY SELECTION AND DATA EXTRACTION: Phase 3 studies plus relevant literature on mirikizumab pharmacologic and clinical profile were reviewed. DATA SYNTHESIS: Mirikizumab approval was based on LUCENT-1 and LUCENT-2. In the phase 3 studies involving patients with moderate to severe UC, mirikizumab, when compared to placebo, resulted in clinical remission in a significantly higher proportion of patients in both the induction and maintenance phase. In addition, mirikizumab met the secondary endpoints of alternate definition of clinical remission, endoscopic remission, glucocorticoid-free clinical remission, histologic-endoscopic mucosal remission, and improvement in bowel urgency status, bowel-urgency remission, and maintenance of clinical remission. Common adverse events noted include infection (15.1%), injection-site reaction (8.7%), nasopharyngitis (7.2%), and headache (3.3%). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING AGENTS: Mirikizumab is the first selective interleukin 23 (IL-23) inhibitor approved for UC. Additional studies are required to determine how to position mirikizumab in both biologic-naïve and biologic-experienced patients with moderate to severe UC. CONCLUSION: Mirikizumab provides a novel mechanism of action for the treatment of moderate to severe UC and is another welcomed treatment advance in the treatment arsenal, providing a more selective mechanism of action while maintaining a comparable safety profile.

Peri-Operative Optimization of Patients with Crohn's Disease.

PURPOSE OF REVIEW: The management of patients with Crohn's disease (CD) undergoing surgery is complex and optimization of modifiable factors perioperatively can improve outcomes. This review focuses on the perioperative management of CD patients undergoing surgery, emphasizing the need for a multi-disciplinary approach. RECENT FINDINGS: Research highlights the benefits of a comprehensive strategy, involving nutritional optimization, psychological assessment, and addressing septic complications before surgery. Despite many CD patients being on immune-suppressing medications, studies indicate that most of these medications are safe to use and should not delay surgery. However, a personalized approach for each case is needed. This review underscores the importance of multi-disciplinary team led peri-operative management of CD patients. We suggest that this can be done at a dedicated perioperative clinic for prehabilitation, with the potential to enhance outcomes for CD patients undergoing surgery.

Biosimilars in IBD: What Every Clinician Needs to Know.

PURPOSE OF REVIEW: Biosimilars were introduced to decrease biologic-related expenditures, but their uptake in inflammatory bowel disease (IBD) remains suboptimal. Herein, we review biosimilar concepts, current products available for IBD treatment, and resources to support biosimilar utilization. RECENT FINDINGS: Although a cornerstone of IBD treatment, biologics are costly due to their development. Biosimilars, which are biologic products highly similar to a reference product, aim to decrease these expenditures. Infliximab, adalimumab, and ustekinumab biosimilars are approved for IBD, but uptake remains low due to biosimilar efficacy and safety concerns and delayed market entry. Clinicians can effectively address some of these barriers and help patients and healthcare systems reap the benefits of decreased costs and increased treatment access. Data shows comparable efficacy and safety outcomes with biosimilars in IBD. Several biosimilar products are available and in the pipeline, but efforts are needed from various stakeholders to bolster utilization and generate benefits.

Etrasimod: A Sphingosine-1-Phosphate Receptor Modulator for the Treatment of Ulcerative Colitis.

OBJECTIVE: To review the pharmacologic and clinical profile of etrasimod in the treatment of ulcerative colitis (UC). DATA SOURCES: A PubMed search was conducted from inception to November 2023 using the keywords etrasimod, ulcerative colitis, and sphingosine-1-phosphate receptor modulator. Information was also obtained from published abstracts and package insert. STUDY SELECTION AND DATA EXTRACTION: Phase 2 and 3 studies plus relevant literature on etrasimod pharmacologic and clinical profile were reviewed. DATA SYNTHESIS: Per ELEVATE, 2 phase 3 studies, a higher proportion of patients with moderately to severely active UC achieved clinical remission in the induction and maintenance phase with etrasimod compared with placebo. In addition, a higher proportion of patients achieved secondary endpoints of clinical response, endoscopic improvement-histologic remission, corticosteroid-free remission, and endoscopic improvement with etrasimod vs placebo. Common adverse events include anemia and headache. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING DRUGS: Etrasimod is now the second orally administered sphingosine-1-phosphate modulator approved for UC, providing patients with additional treatment options. Efficacy rates of this treatment are in line with other UC medication options. Similar to other sphingosine-1-phosphate receptor modulators, various assessments are required at baseline and during treatment to ensure safe and appropriate use. CONCLUSION: Etrasimod is another possibility in the armamentarium of UC treatment, providing patients with more oral medication options. Prior to treatment initiation, several assessments relating to safety, drug interactions, and pharmacogenomics factors are advised.

Defining the Roles of Inflammatory Bowel Disease Clinical Pharmacists in the United States: A Systematic Review and National RAND/UCLA Consensus.

BACKGROUND: Given the complexity of inflammatory bowel disease (IBD) care, utilization of multidisciplinary teams is recommended to optimize outcomes. There is a growing recognition that clinical pharmacists should be an integral part of this care model. We sought to define the roles of IBD clinical pharmacists in the United States. METHODS: A national multidisciplinary expert panel of 12 gastroenterologists and clinical pharmacists practicing in IBD clinics was assembled. We used the RAND/University of California, Los Angeles appropriateness method, with a total of 281 statements generated based on a systematic literature review and expert opinion. Each statement was anonymously rated as appropriate, uncertain, or inappropriate in 2 rounds of voting. RESULTS: The number of publications evaluating the clinical pharmacists' roles in IBD is limited, primarily focusing on thiopurine initiation and monitoring, medication adherence, and switching to biosimilars. Medication education; medication initiation and monitoring; therapeutic drug monitoring; biosimilar management; health maintenance review; and transitions of care were deemed by the panel to be appropriate roles for IBD clinical pharmacists. In considering real-world settings, IBD clinical pharmacists should practice clinically under a predefined scope and primarily focus on complex treatments (eg, immunomodulators, biologics, and small molecules). Clinical pharmacists should also be included in practice settings with IBD specialized physicians. Additionally, clinical pharmacists caring for patients with IBD should be residency trained and board certified. CONCLUSIONS: This consensus defines IBD clinical pharmacists' roles and provides a framework for embedded clinical pharmacists in IBD care.

Safety and Monitoring of Inflammatory Bowel Disease Advanced Therapies.

The recent approval of new medications with novel mechanisms of action and emergence of updated safety information for existing therapies has changed the treatment landscape of inflammatory bowel disease (IBD). These advances led to unique adverse effect profiles and identification of new safety signals, resulting in the evolution of the safety, monitoring, and positioning of IBD therapies. In this updated review, we (1) examine the existing and updated safety data of monoclonal antibodies and small molecules for IBD, with a focus on recently Food and Drug Administration (FDA)-approved therapies, and (2) propose risk stratification and assessment considerations prior to and during IBD treatment.

Preparing for the market entry of adalimumab biosimilars in the US in 2023: A primer for specialty pharmacists.

PURPOSE: The impact of the market entry of adalimumab biosimilars on clinical practices and specialty pharmacies is explained. A roadmap is also provided for how pharmacists can successfully navigate this landscape. SUMMARY: Biosimilars have previously been introduced as a mechanism to help curb biologic expenditures, with biosimilars undergoing an abbreviated regulatory approval process that focuses on biosimilarity and generating product competition. Adalimumab is currently the leading product in the biologics market, generating approximately $20 to $30 billion in sales worldwide consecutively from 2019 to 2021. Many adalimumab biosimilars are slated to enter the market in 2023 and become available for patient use. However, compared to other biosimilars, adalimumab biosimilars have several unique considerations, such as interchangeability and concentration, that will impact pharmacy practices and workflows. Because pharmacists embedded in clinical practices and specialty pharmacies will be significantly involved in the processes relating to adalimumab biosimilar implementation, adoption, and use, a primer on understanding the various adalimumab biosimilar products available and considerations surrounding these products with regard to workflow and patient use is critical. Several resources are also provided to help pharmacists successfully navigate the adalimumab biosimilar landscape. CONCLUSION: The biosimilar landscape continues to evolve, and 2023 will see the launch of several adalimumab biosimilar products, which vary with regard to formulation, concentration, and interchangeability status. Pharmacists are well positioned to educate providers and patients about this landscape and help implement an efficient workflow to support adalimumab biosimilar adoption and use.

Risankizumab-rzaa: A New Therapeutic Option for the Treatment of Crohn's Disease.

OBJECTIVE: To review the pharmacologic and clinical profile of risankizumab-rzaa in the treatment of Crohn's disease (CD). DATA SOURCES: A PubMed search was performed from inception to August 2022 using keywords risankizumab, risankizumab-rzaa, interleukin-23 inhibitor, and Crohn's disease. Information was obtained from package inserts as well as published abstracts. STUDY SELECTION AND DATA EXTRACTION: Phase 2 and 3 studies plus relevant literature on risankizumab-rzaa pharmacologic and clinical profile were reviewed. DATA SYNTHESIS: Risankizumab-rzaa approval was based on ADVANCE, MOTIVATE, and FORTIFY. In these 3 phase 3 studies involving patients with moderate to severe CD, risankizumab-rzaa, when compared with placebo, resulted in clinical remission and endoscopic response in a significantly higher proportion of patients in both the induction and maintenance phase. In addition, risankizumab-rzaa met the secondary endpoints of clinical response, endoscopic improvement, corticosteroid-free remission, and mucosal healing. Common adverse events noted include nasopharyngitis, arthralgia, headache, abdominal pain, and nausea. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Risankizumab-rzaa is the first selective IL-23 inhibitor approved for CD and provides an additional therapeutic option for patients, particularly those who have been previously treated with other advanced inflammatory bowel disease therapies. Additional studies are required to determine how to best position risankizumab-rzaa in both bio-naïve and bio-experienced patients with CD. CONCLUSIONS: Risankizumab-rzaa is the most recent therapeutic advance for CD. It has a selective mechanism of action with a similar safety profile comparable with other currently approved advanced therapies.

Hypoxia-Inducible Factor 1-Alpha Stabilizers in the Treatment of Inflammatory Bowel Diseases: Oxygen as a Novel IBD Therapy?

Despite the significant advances in the medical armamentarium for inflammatory bowel diseases [IBD], current treatment options have notable limitations. Durable remission rates remain low, loss of response is common, administration routes are largely parenteral for novel biologics, and medication safety remains a concern. This explains an ongoing unmet need for safe medications with novel mechanisms of action that are administered orally. In line with these criteria, hypoxia-inducible factor [HIF]-1α stabilizers, acting via inhibition of prolyl hydroxylase enzymes, are emerging as an innovative therapeutic strategy. We herein review the mechanism of action and available clinical data for HIF-1α stabilizers and their potential place in the future IBD treatment algorithm.

Adalimumab-Adbm: The First Interchangeable Biosimilar for the Treatment of Inflammatory Diseases.

OBJECTIVE: The objective of the study was to review the pharmacologic and clinical profile of adalimumab-adbm (BI 695501), the first interchangeable biosimilar for treatment of inflammatory diseases. DATA SOURCES: A PubMed search was conducted from inception to December 2021 using the keywords BI 695501 and adalimumab-adbm. Information was also obtained from published abstracts and package inserts. STUDY SELECTION AND DATA EXTRACTION: Phase 1, 2 and 3 studies plus relevant literature on adalimumab-adbm pharmacologic and clinical profile were reviewed. DATA SYNTHESIS: Adalimumab-adbm approval was based on a series of phase 3 VOLTAIRE trials, which evaluated the biosimilar's efficacy and safety in the treatment of moderate to severe Crohn's disease, rheumatoid arthritis, and psoriasis. Interchangeability status was granted based on data from the VOLTAIRE-X trial. The VOLTAIRE and VOLTAIRE-X studies demonstrated comparable efficacy and safety between adalimumab-adbm and reference adalimumab. Common adverse events included infections and injection site reactions. Similar to reference adalimumab, adalimumab-adbm contains black box warnings related to serious infections and malignancy. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Adalimumab-adbm is the first interchangeable biosimilar to be approved for inflammatory diseases and has the potential to improve patient access to treatment while decreasing medication-related costs. However, it will not be commercially available for patient use until 2023 and its adoption into clinical practice may face potential barriers seen with other biosimilars. CONCLUSION: As an interchangeable biosimilar with comparable efficacy and safety to reference adalimumab, adalimumab-adbm is an important advance toward cost-effective management of inflammatory diseases.

The Sincerest Form of Flattery? Biosimilars in Inflammatory Bowel Disease.

Biosimilar medications have the potential to significantly reduce the cost of treatment in patients with inflammatory bowel disease. Observational studies have shown similar efficacy and safety of biosimilars to biologic reference products. Shared decision-making is crucial to the successful implementation of these agents.

Core functions and forms of Bright IDEAS: A multi-methods evaluation of the adoption of an evidence-based psychosocial training program through iterative adaptation.

Background: Despite efforts to widely disseminate interventions designed to increase access to quality supportive care to pediatric cancer patients and their families, many of these interventions fail to meet expectations once deployed in real-life clinical settings. This study identifies the functions and forms of Bright IDEAS: Problem-Solving Skills Training, an evidence based psychosocial intervention for caregivers of children recently diagnosed with cancer, to identify pragmatic program adaptations in its real-world clinical implementation. We compare intervention adoption before and after adaptations to the Bright IDEAS training program as part of a national training program designed to disseminate the intervention. Methods: 209 pediatric psychosocial oncology practitioners representing 134 unique institutions were trained during 10 in-person 8-hour workshops (2015-2019). Functions and forms of Bright IDEAS were identified, and adaptations made to the training agenda and curriculum based on practitioner feedback following implementation in local institutions. Mixed method evaluation included longitudinal surveys at 6- and 12-months post training; and qualitative interviews among a subgroup of practitioners (N = 47) to understand and compare perspectives on intervention adoption and barriers to implementation before and after adaptations to the Bright IDEAS training program. The RE-AIM framework was used to guide dissemination evaluation. Results: A total of four adaptations were tailored to the identified forms of the intervention: case studies; pre-training reading materials; training videos; and letters of institutional support from primary supervisor. Pre- and post-training adaptations to the Bright IDEAS training program were mapped to RE-AIM constructs. Quantitative findings demonstrate that adaptations appeared to improve adoption and usage overall. Conclusion: This study provides insight into how contextual factors influence psychosocial practitioners' capacity to adopt, implement, and maintain Bright IDEAS in the clinical setting. This study demonstrates the use of real-time stakeholder feedback to guide intervention translation from research to practice settings.

Ozanimod: A First-in-Class Sphingosine 1-Phosphate Receptor Modulator for the Treatment of Ulcerative Colitis.

OBJECTIVE: To review the pharmacological and clinical profile of ozanimod in the treatment of ulcerative colitis (UC). DATA SOURCES: A PubMed search was conducted from inception to July 2021 using the keywords ozanimod, ulcerative colitis, and sphingosine 1-phosphate receptor modulator. Information was also extracted from published abstracts and the package insert. STUDY SELECTION AND DATA EXTRACTION: Phase 2 and 3 studies and relevant literature on ozanimod pharmacological and clinical profiles were reviewed. DATA SYNTHESIS: Ozanimod approval was based on True North, a phase 3 trial evaluating ozanimod's efficacy and safety in the treatment of moderate to severe UC. Compared with placebo, ozanimod led to clinical remission in a significantly higher proportion of patients in both the induction and maintenance phase. Additionally, for secondary end points of clinical response, endoscopic improvement, corticosteroid-free remission, and mucosal healing, ozanimod performed significantly better than placebo. Common adverse events included infections, headaches, hypertension, bradycardia, and liver enzyme elevations. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Ozanimod is the first sphingosine 1-phosphate modulator to be approved for UC and is administered orally. Its efficacy profile is comparable with other UC medications. However, its safety profile is unique, requiring extensive assessments prior to initiation of and during treatment. Thus, it is unclear how ozanimod will be positioned in UC treatment. CONCLUSION: Ozanimod is another option in the growing arsenal of UC treatment. Although it offers a novel mechanism of action and is administered orally, there are important safety, dosing, and pharmacokinetic factors to consider prior to initiation and use.

Pharmacist-Managed Helicobacter pylori Treatment Service Within a Gastroenterology Clinic: Workflow and Real-World Experiences.

BACKGROUND: Treatment eradication rates of Helicobacter pylori, a gastrointestinal infection, are 70% to 90% in clinical studies but lower in real-world settings. Potential barriers include multidrug regimen complexity or prescribing/administration errors. A pharmacist-managed H pylori treatment service was implemented to address these barriers and optimize treatment outcomes. The clinical pharmacist provided 2 services: (1) treatment education and monitoring for treatment-naïve patients and (2) treatment initiation, education, and monitoring for treatment-experienced patients. OBJECTIVE: We aimed to evaluate the impact of a pharmacist-managed H pylori treatment service within a gastroenterology clinic. METHODS: We conducted a retrospective observational cohort study of all patients referred to and seen in the pharmacist-managed H pylori treatment service from July 10, 2019, to December 31, 2020. Patient demographics, prior treatment history, course(s) of treatment prescribed, frequency of follow-ups, and outcomes posttreatment were collected. RESULTS: The clinical pharmacist managed 60 referrals for 55 unique patients over a mean of 5 ± 2 visits. Five patients failed H pylori treatment and were re-referred. Identified barriers included prescribing/dispensing and administration errors. Posttreatment, 38 referrals tested for H pylori eradication, of which 100% of treatment-naïve patients and 69% of treatment-experienced patients were cured, and 13 (22%) referrals were lost to follow-up. CONCLUSION AND RELEVANCE: This study described and assessed the impact of a pharmacist-managed H pylori treatment service in a gastroenterology clinic, in which various barriers were effectively addressed to optimize treatment outcomes. Future studies should focus on long-term outcome, impact on health care costs, and patient satisfaction with this service.

Safety of Rapid Infliximab Biosimilar Infusions in Patients With Inflammatory Bowel Disease.

BACKGROUND: The biosimilar landscape for inflammatory bowel disease (IBD) continues to grow, with several biosimilar products for originator infliximab now available. The rapid infusion of originator infliximab and infliximab-dyyb has been shown to be well tolerated; however, the tolerability of rapid infusion in patients receiving infliximab-abda, another infliximab biosimilar, or in those who have switched among originator infliximab and biosimilars remains unknown. OBJECTIVE: We aimed to evaluate the safety of rapid infusion in patients with IBD who received infliximab-abda or underwent switches with infliximab products. METHODS: We conducted a retrospective observational study of all infliximab-related infusion encounters for patients ≥18 years with IBD who received their infusion over 30 to 90 minutes at our institution between March 1, 2020, and September 30, 2020. Patient, disease, and treatment characteristics were collected. The primary outcome was infusion reactions. RESULTS: A total of 377 infusion encounters for 96 unique patients were evaluated. Within the study cohort, 16% of patients were treated with originator infliximab, 42% with infliximab-dyyb, and 2% with infliximab-abda. The remaining 41% of patients received at least 2 infliximab products during the study period, primarily infliximab-dyyb and infliximab-abda. Approximately 54% and 42% of infusions encounters included premedication and immunomodulator use. Within the 377 infusion encounters, no infusion reactions were noted. CONCLUSION AND RELEVANCE: Rapid infusion of infliximab biosimilars (including infliximab-abda) and in patients who have switched among originator infliximab and biosimilars is well tolerated. Future studies should assess clinical impact and outcomes of rapid infusion with biosimilars.

COVID-19 vaccine use in immunocompromised patients: A commentary on evidence and recommendations.

PURPOSE: While COVID-19 vaccine emergency use authorization (EUA) deemed the vaccines to be effective and safe for public use, the phase 3 trials leading to EUA predominantly excluded patients with immunocompromising conditions. Immunocompromised patients make up a significant proportion of the population, and in light of recent mass vaccination efforts, we aim to review current evidence and recommendations of COVID-19 vaccines in 4 patient populations with immunocompromising disorders or conditions: human immunodeficiency virus (HIV) infection, solid organ transplantation, rheumatoid arthritis, and inflammatory bowel disease. SUMMARY: Given the evolving data on the safety and efficacy of the approved COVID-19 vaccines in the immunocompromised population, it is vital that pharmacists and other immunizing providers understand the current data and recommendations and provide the public with accurate information. To date, the only immunocompromised subgroup included in phase 3 COVID-19 vaccine trials have been those with HIV infection. However, recent retrospective trials have provided reassuring data on the safety of the COVID-19 vaccine in immunocompromised patients, and the interim analysis of the Moderna phase 3 trial produced promising data on efficacy in HIV-infected patients. Presently, the US Centers for Disease Control and Prevention, British Society for Immunology, and various other governmental and professional societies and organizations endorse COVID-19 vaccination in the immunocompromised population. CONCLUSION: While additional data is needed to determine the effects of immunocompromising medical conditions and immunosuppressing medications on the efficacy of the vaccine, the benefits of vaccination is anticipated to outweigh theoretical risks. Thus, COVID-19 vaccination is recommended for immunocompromised patients at this time, and providers should make efforts to decrease vaccine hesitancy in this population through education and reassurance.

An evaluation of clinical decision support tools for Patient Health Questionnaire-9 administration.

INTRODUCTION: Many health care institutions are working to improve depression screening and management with the use of the Patient Health Questionnaire 9 (PHQ-9). Clinical decision support (CDS) within the EHR is one strategy, but little is known about effective approaches to design or implement such CDS. The purpose of this study is to compare implementation outcomes of two versions of a CDS tool to improve PHQ-9 administration for patients with depression. METHODS: This was a retrospective, observational study comparing two versions of a CDS. Version 1 interrupted clinician workflow, and version 2 did not interrupt workflow. Outcomes of interest included reach, adoption, and effectiveness. PHQ-9 administration was determined by chart review. Chi-square tests were used to evaluate associations between PHQ-9 administration with versions 1 and 2. RESULTS: Version 1 resulted in PHQ-9 administration 77 times (15.3% of 504 unique encounters) compared with 49 times (9.8% of 502 unique encounters) with version 2 (P = .011). DISCUSSION: An interruptive CDS tool may be more effective at increasing PHQ-9 administration, but a noninterruptive CDS tool may be preferred to minimize alert fatigue despite a decrease in effectiveness.