Ulcerative colitis (UC) is an idiopathic inflammatory disorder. These guidelines indicate the preferred approach to the management of adults with UC and represent the official practice ...recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the evidence was not appropriate for GRADE, but there was consensus of significant clinical merit, "key concept" statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios.
Medications are available that can be highly effective for the treatment of inflammatory bowel disease (IBD). However, there are multiple barriers in place to offer these treatments to the right ...patients at the right time. In addition to obstacles created by payers, there are concerns over medication side effects by patients and providers, and the logistic challenges of navigating the maze of initiating someone on biological therapy. As a gastroenterology community, we need to push the field forward for the sake of our patients. Current and future drug development for IBD is exciting, but we need to optimize what we have now to the best of our ability. When used appropriately and early enough in the disease course, our current medications can heal the bowel and prevent complications from developing. While recognizing that all patients do not need early intensive therapy, we need to identify the appropriate patients for more aggressive treatments. This article will describe how we can improve patient management now by shifting our focus to using a personalized, proactive, and patient-centered approach in our delivery of IBD care.
Abstract Healthcare is changing rapidly, so we must change with the times to develop more efficient, practical, cost-effective and, importantly, high-quality methods to care for patients. We teach ...medial students that optimal patient care requires face to face interactions, to collect information on patients’ history, and the physical examination. However, management of many patients—especially those with chronic diseases—does not always require physical examination. Telemedicine offers an opportunity to take advantage of technology while leveraging the progressive push towards efficiency and value, but also requires the belief that excellent patient care is not always provided in person. Telemedicine can include a variety of aspects of patient care adapted to be performed remotely, such as telemonitoring, tele-education, teleconsulting, and telecare. All of these have been evaluated in gastroenterology practice and have demonstrated feasibility and patient preference, but have produced mixed results regarding patient outcomes. By combining telemedicine tools and new care models, we can redesign chronic disease management to include fewer in-person visits when patients are well, yet increase access for patients who need to be seen. This change could lead to higher-value care, by improving the experience of care, decreasing costs, and improving health of the population. Barriers include reimbursement, licensing, and fear of litigation. However, if we hope to meet the needs of patients within our changing healthcare system, telemedicine should be incorporated into our strategy.
The treatment of inflammatory bowel disease is becoming more complicated with new medications and new treatment paradigms. Although data are accumulating that the earlier use of immunomodulators and ...anti-tumor necrosis factor agents are more effective than the standard "step-up" pyramidal treatment algorithm, patients may not be comfortable with this more intensive therapeutic approach. The process of shared decision making engages patients in treatment decisions to optimize the chance that a chosen therapy matches their personal preferences for care. Decision aids are standard shared decision making tools, which are used to present evidence-based data in a patient-friendly manner to help patients with preference-sensitive decisions. Not all care decisions are preference-sensitive, and not all patients are interested in being part of a shared medical decision. The responsibility of the provider is to identify how much of a role patients want, and then determine which decisions need their input to provide the best patient-centered care. The overall goal is to involve patients in decisions so that they are educated about their options, confident in the plan, adherent to chosen therapy and ultimately have a better quality of life.
Background & Aims Multiple randomized controlled trials (RCTs) have been conducted to determine therapeutic efficacy of the biological agents for the inflammatory bowel diseases (IBD). However, the ...external validity of findings from RCTs might be compromised by their stringent selection criteria. We investigated the proportion of patients encountered during routine clinical practice who would qualify for enrollment into a pivotal RCT of biological agents for IBD. Methods We performed a retrospective cohort study of adult patients with moderate–severe IBD who presented to a tertiary referral center. Inclusion and exclusion criteria were extracted from published RCTs of biologics approved by the Food and Drug Administration and applied to the study population. Results Only 31.1% of 206 patients with IBD (34% with Crohn's disease CD, 26% with ulcerative colitis) would have been eligible to participate in any of the selected RCTs. Patients would have been excluded because they had stricturing or penetrating CD, took high doses of steroids, had comorbidities or prior exposure to biologics, or received topical therapies. Of the trial-ineligible patients with ulcerative colitis, 23.3% had colectomies, and 31.7% received infliximab, with a 63.2% response rate. Approximately half (49.4%) of the 82 trial-ineligible patients with CD received biological therapies, with lower response rates (60%) than trial-eligible patients (89%; P = .03). Conclusions Most patients with moderate–severe IBD evaluated in an outpatient practice would not qualify for enrollment in a pivotal RCT of biological reagents; this finding raises important questions about their therapeutic efficacy beyond the clinical trial populations. Additional evaluation of the transparency of RCT design and selection criteria is needed to determine whether trial results can be generalized to the population.
Therapeutic drug monitoring (TDM) of biologics is a rapidly evolving field. We aimed to provide a consensus statement regarding the clinical utility of TDM for biologics in inflammatory bowel disease ...(IBD). A modified Delphi method was applied to develop consensus statements. A comprehensive literature review was performed regarding TDM of biologic therapies in IBD, and 45 statements were subsequently formulated on the potential application of TDM in IBD. The statements, along with literature, were then presented to a panel of 10 gastroenterologists with expertise in IBD and TDM who anonymously rated them on a scale of 1-10 (1 = strongly disagree and 10 = strongly agree). An expert consensus development meeting was held virtually to review, discuss, refine, and reformulate statements that did not meet criteria for agreement or that were ambiguous. During the meeting, additional statements were proposed. Panelists then confidentially revoted, and statements rated ≥7 by 80% or more of the participants were accepted. During the virtual meeting, 8 statements were reworded, 7 new statements were proposed, and 19 statements were rerated. Consensus was finally reached in 48/49 statements. The panel agreed that reactive TDM should be used for all biologics for both primary nonresponse and secondary loss of response. It was recommended that treatment discontinuation should not be considered for infliximab or adalimumab until a drug concentration of at least 10-15 μg/mL was achieved. Consensus was also achieved regarding the utility of proactive TDM for anti-tumor necrosis factor therapy. It was recommended to perform proactive TDM after induction and at least once during maintenance. Consensus was achieved in most cases regarding the utility of TDM of biologics in IBD, specifically for reactive and proactive TDM of anti-tumor necrosis factors.
Telemedicine can take a number of forms. A popular approach is the use of telemonitoring, which takes advantage of available technology to follow patients remotely. Cross and colleagues present the ...results of a well-done randomized controlled trial to assess the impact of a telemonitoring program for patients with inflammatory bowel disease. They did not show a difference in disease activity, but this study leads us to question whether we know the appropriate outcomes to follow for telemedicine interventions. If we can show that telemedicine maintains quality of care at lower costs, the value of these types of interventions will ultimately be increased.
We assessed the real-world effectiveness and safety of vedolizumab (VDZ) in moderate-severe Crohn's disease (CD).
Retrospective cohort study of seven medical centers, from May 2014 to December 2015. ...Adults with moderate-severe CD treated with VDZ, with follow-up after initiation of therapy, were included. Using the multivariable Cox proportional hazard analyses, we identified independent predictors of clinical remission or mucosal healing with VDZ. Rates of serious infection (requiring antibiotics, resulting in discontinuation of VDZ, hospitalization or death) and serious adverse events (discontinuation of VDZ, hospitalization or death) were described quantitatively.
We included 212 patients with moderate-severe CD (median age 34 years; 40% male; 90% tumor necrosis factor (TNF)-antagonist exposed) with a median follow-up (IQR) of 39 weeks (25-53). Twelve-month cumulative rates of clinical remission, mucosal healing, and deep remission (clinical remission+mucosal healing) were 35%, 63%, and 26%, respectively. Individuals with prior TNF-antagonist exposure (hazard ratio (HR) 0.40; 95% confidence interval (CI): 0.20-0.81), smoking history (HR 0.47; 95% CI: 0.25-0.89), active perianal disease (HR 0.49; 95% CI: 0.27-0.88), and severe disease activity (HR 0.54; 95% CI: 0.31-0.95) were less likely to achieve clinical remission. Those with prior TNF-antagonist exposure (HR 0.29; 95% CI: 0.12-0.73), and severe disease activity (HR 0.54; 95% CI: 0.31-0.95) were less likely to achieve mucosal healing. During 160 patient years of follow-up (PYF) and 1,433 VDZ infusions, 5 patients developed infusion reactions (3.5 per 1,000 infusions), 21 developed serious infections (13 per 100 PYF), and 17 developed serious adverse events (10 per 100 PYF). A minority of adverse events required discontinuation of therapy (6 per 100 PYF).
VDZ is a safe and effective treatment option for moderate-severe CD in routine practice. Clinical remission and deep remission (clinical remission and mucosal healing) can be achieved in 1/3 of individuals, and a minority of individuals require discontinuation of therapy due to adverse events.
Background & Aims There is controversy regarding the best treatment for patients with Crohn’s disease because of the lack of direct comparative trials. We compared therapies for induction and ...maintenance of remission in patients with Crohn’s disease, based on direct and indirect evidence. Methods We performed systematic reviews of MEDLINE, EMBASE, and Cochrane Central databases, through June 2014. We identified randomized controlled trials (N = 39) comparing methotrexate, azathioprine/6-mercaptopurine, infliximab, adalimumab, certolizumab, vedolizumab, or combined therapies with placebo or an active agent for induction and maintenance of remission in adult patients with Crohn’s disease. Pairwise treatment effects were estimated through a Bayesian random-effects network meta-analysis and reported as odds ratios (OR) with a 95% credible interval (CrI). Results Infliximab, the combination of infliximab and azathioprine (infliximab + azathioprine), adalimumab, and vedolizumab were superior to placebo for induction of remission. In pair-wise comparisons of anti–tumor necrosis factor agents, infliximab + azathioprine (OR, 3.1; 95% CrI, 1.4–7.7) and adalimumab (OR, 2.1; 95% CrI, 1.0–4.6) were superior to certolizumab for induction of remission. All treatments were superior to placebo for maintaining remission, except for the combination of infliximab and methotrexate. Adalimumab, infliximab, and infliximab + azathioprine were superior to azathioprine/6-mercaptopurine: adalimumab (OR, 2.9; 95% CrI, 1.6–5.1), infliximab (OR, 1.6; 95% CrI, 1.0–2.5), infliximab + azathioprine (OR, 3.0; 95% CrI, 1.7–5.5) for maintenance of remission. Adalimumab and infliximab + azathioprine were superior to certolizumab: adalimumab (OR, 2.5; 95% CrI, 1.4–4.6) and infliximab + azathioprine (OR, 2.6; 95% CrI, 1.3–6.0). Adalimumab was superior to vedolizumab (OR, 2.4; 95% CrI, 1.2–4.6). Conclusions Based on a network meta-analysis, adalimumab and infliximab + azathioprine are the most effective therapies for induction and maintenance of remission of Crohn’s disease.
Immunomodulators and biological agents are effective for the treatment of ulcerative colitis and Crohn's disease; however, there is concern that these therapies may be associated with an increased ...risk of malignancy. MEDLINE, Cochrane Library, and Web of Science were searched for articles regarding these medications and their associations with hematologic malignancies and solid tumors in inflammatory bowel diseases (IBDs) and transplant, rheumatology, dermatology, and neurology patient populations. There is evidence that use of thiopurines and anti-tumor necrosis factor (TNF) agents is associated with an increased risk of lymphoma, particularly non-Hodgkin's lymphoma in patients with IBD. Hepatosplenic T-cell lymphoma, although rare, also occurs with increased frequency in patients treated with thiopurines and anti-TNF medications, and young male patients with Crohn's disease appear to be at greatest risk. Furthermore, thiopurines and anti-TNF agents are associated with elevated rates of nonmelanoma skin cancer in non-IBD and IBD patients, and anti-TNF agents may also increase the risk of melanoma. Rates of abnormal cervical cytology may be elevated by the use of immunosuppressive agents in female patients with IBD. There is little evidence that exposure to the therapeutic agents prescribed for IBD increases the risk of any other solid tumors or hematologic malignancies in non-IBD or IBD patients. Although the use of immunomodulators and anti-TNF agents can promote certain types of lymphoma and skin cancer, patients and clinicians should be aware that the absolute rates of these malignancies remain low, and these risks should be weighed carefully against the substantial benefits offered by these therapies.
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