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.

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.

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.

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.

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.

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.

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.

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.

Does Similarity Breed Contempt? A Review of the Use of Biosimilars in Inflammatory Bowel Disease.

The introduction of therapeutic monoclonal antibodies directed against tumor necrosis factor-α has revolutionized the treatment of inflammatory bowel disease (IBD) by improving quality of life, decreasing the frequency and length of hospital admissions, and reducing corticosteroid use. Nevertheless, biologics are very expensive, substantially contributing to the cost of care for patients with IBD. To reduce this cost and improve treatment access, biosimilars, which are therapeutic monoclonal antibodies (biologicals) similar to but not identical to the reference biologic, were introduced. Despite their potential benefits, the adoption and uptake of biosimilars have varied considerably across the USA and Europe. Here, we highlight the current biosimilar therapeutic landscape, discuss barriers to their use, and provide an overview of published studies evaluating the efficacy and safety of biosimilars in IBD.

Impact of Clinical Pharmacists in Inflammatory Bowel Disease Centers During the COVID-19 Pandemic.

INTRODUCTION: To characterize the clinical pharmacists' impact on caring for patients with inflammatory bowel disease during COVID-19. METHODS: A clinical pharmacist's encounters between March 17 and April 14, 2020, were audited to determine encounter frequency and indication. RESULTS: The clinical pharmacist addressed COVID-19 and inflammatory bowel disease treatment concerns with 140 patients, conducted 34 medication education and monitoring visits, reviewed 141 patients' charts and helped rescheduled 18 patients who missed their biologic infusion, transitioned 12 patients to home infusions, and assisted 5 patients with medication access. DISCUSSION: Clinical pharmacists embedded in gastroenterology practices permit for continued optimal patient care during a pandemic.

Factors influencing the acceptance of referrals for clinical pharmacist managed disease states in primary care.

OBJECTIVE: Clinical pharmacists use population health methods to generate chronic disease management referrals for patients with uncontrolled chronic conditions. The purpose of this study was to compare primary care providers' (PCPs) referral responses for 4 pharmacist-managed indications and to identify provider and patient characteristics that are predictive of PCP response. DESIGN: Retrospective cohort study. SETTING: This study occurred in an academic internal medicine clinic. PARTICIPANTS: Clinical pharmacy referrals generated through a population health approach between 2012 and 2016 for hypertension, chronic pain, depression, and benzodiazepine management were included. MAIN OUTCOME MEASURES: Proportion of referrals accepted, left pending, or rejected and influencing provider and patient characteristics. RESULTS: Of 1769 referrals generated, PCPs accepted 869 (49%), left pending 300 (17%), and rejected 600 (34%). Compared with referrals for hypertension, benzodiazepine management, and depression, chronic pain referrals had the lowest likelihood of rejection (odds ratio [OR] 0.31; 95% CI 0.19-0.49). Depression referrals had an equal likelihood of being accepted or rejected (OR 1.04; 95% CI 0.66-1.64). Provider characteristics were not significantly associated with referral response, but residents were more likely to accept referrals. Patient characteristics associated with lower referral rejection included black race (OR 0.39; 95% CI 0.18-0.87), higher systolic blood pressure (OR 0.98; 95% CI 0.97-0.99), and missed visits (OR 0.24; 95% CI 0.07-0.81). CONCLUSION: The majority of referrals for clinical pharmacists in primary care settings were responded to, varying mostly between acceptance and rejection. There was variability in referral acceptance across indications, and some patient characteristics were associated with increased referral acceptance.

Outcomes of a Pharmacist-Managed Heart Failure Medication Titration Assistance Clinic.

BACKGROUND: National guidelines recommend angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) and ß-blockers (BBs) at target doses for morbidity and mortality benefits in heart failure with reduced ejection fraction (HFrEF); regardless, titration of these therapies in practice remains suboptimal. We implemented an outpatient pharmacist-managed HFrEF medication titration assistance clinic (MTAC) at one institution to improve titration for general cardiology (GC) patients. OBJECTIVE: To evaluate MTAC impact by determining the proportion of patients on target or maximum tolerated ACE inhibitor/ARB and BB doses. METHODS: A retrospective chart review of adult patients with documented ejection fraction ≤40% managed in the MTAC or GC from 2011 to 2013 was conducted. HFrEF medication regimens were collected at initial visit and months 1, 2, 3, 6, 9, and 12 to assess titration. Target doses were defined per guideline or dose at which ejection fraction recovered during the study. Maximum tolerated doses were defined as the highest dose patients tolerated without physiological limitations. RESULTS: Of 148 patients, the MTAC managed 51 and GC managed 97. At baseline, 90% of MTAC versus 82% of GC patients were prescribed ACE inhibitors/ARBs and BBs. In the MTAC, 4% were at target or maximum tolerated doses compared with 32% of GC patients ( P < 0.001). At 12 months, 95% of patients in the MTAC and 87% in GC were prescribed ACE inhibitors/ARBs and BBs. Of those prescribed ACE inhibitors/ARBs and BBs, 64% in the MTAC versus 40% in GC reached target or maximum tolerated doses ( P = 0.01). CONCLUSIONS: The pharmacist-managed MTAC increased the proportion of patients on optimal HFrEF therapies and are a resource for GC patients.

Designing and validation of a yoga-based intervention for obsessive compulsive disorder.

Some yoga-based practices have been found to be useful for patients with obsessive compulsive disorder (OCD). The authors could not find a validated yoga therapy module available for OCD. This study attempted to formulate a generic yoga-based intervention module for OCD. A yoga module was designed based on traditional and contemporary yoga literature. The module was sent to 10 yoga experts for content validation. The experts rated the usefulness of the practices on a scale of 1-5 (5 = extremely useful). The final version of the module was pilot-tested on patients with OCD (n = 17) for both feasibility and effect on symptoms. Eighty-eight per cent (22 out of 25) of the items in the initial module were retained, with modifications in the module as suggested by the experts along with patients' inputs and authors' experience. The module was found to be feasible and showed an improvement in symptoms of OCD on total Yale-Brown Obsessive-Compulsive Scale (YBOCS) score (p = 0.001). A generic yoga therapy module for OCD was validated by experts in the field and found feasible to practice in patients. A decrease in the symptom scores was also found following yoga practice of 2 weeks. Further clinical validation is warranted to confirm efficacy.

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.

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.