Predictors of Patient-Assessed Illness Severity in IBS
Predictors of Patient-Assessed Illness Severity in IBS
Background: Conceptual models suggest that “irritable bowel syndrome (IBS) severity” is a multidimensional outcome that is related to, yet distinct from, health-related quality of life (HRQOL). Existing severity questionnaires are largely based on physician rather than patient-based ratings. Since severity is a patient-centered outcome, it is essential that future instruments are based on patients' self-perceptions of severity. We measured patient-derived predictors of severity in a large cohort of IBS patients.
Methods: We performed a cross-sectional analysis in 755 IBS patients recruited at a university-based center. Subjects completed a bowel symptom questionnaire, SCL-90, and SF-36. The main outcome was patient-assessed “overall severity of gastrointestinal symptoms,” as measured on a 0–20 scale (20 = most severe). We first developed a conceptual model of IBS, and then performed bivariate analyses to identify biopsychosocial predictors of severity. We then entered significant predictors into a multivariable model to measure the independent association of each predictor with severity.
Results: Six factors predicted severity: (a) abdominal pain rating (P < 0.001); (b) belief that “something serious is wrong with body” (P < 0.001); (c) straining with defecation (P= 0.001); (d) myalgias (P= 0.02); (e) urgency with defecation (P= 0.03); and (f) bloating (P= 0.05). Severity correlated highly with HRQOL in bivariate, but not multivariate, analysis.
Conclusion: Patient-derived severity in IBS is related to, yet distinct from, generic HRQOL. IBS severity is predicted by abdominal pain, bloating, straining, urgency, myalgias, and disease-related concern. These symptoms fall along both poles of the “brain-gut axis,” indicating that a full assessment of patient severity must include a balanced biopsychosocial history.
Irritable bowel syndrome (IBS) is a disorder of dysregulated brain-gut homeostasis primarily characterized by gastrointestinal symptoms such as abdominal pain, bloating, and altered bowel habits. Yet many patients also may have concurrent extraintestinal symptoms and disease-specific fears and concerns. The heterogeneity of symptom expression suggests that underlying disease mechanisms vary from patient to patient. Experienced clinicians have observed that some IBS patients appear more “brain than gut” in their disease expression, whereas others are more “gut than brain.” The former group may have underlying somatization, catastrophizing, allostatic overload, and maladaptive coping as central mechanisms of disease expression. The latter group may have abnormal motility, imbalanced intestinal flora, or dysregulated intestinal immunity or inflammation as predominant features. Moreover, although the “brain versus gut” dichotomy may have utility in helping clinicians to stratify patients and develop treatment plans, it is more likely that there are not such clearly defined categories, and instead patients have varying combinations of all these proposed mechanisms.
Despite the heterogeneity of disease mechanisms and expressions, the current clinical paradigm is to adhere all patients with the same IBS label, as recommended by the Rome III committee. In the absence of valid and reliable biomarkers to accurately stratify patients within the broader IBS group, clinicians are left interpreting patient-reported symptoms to determine the diagnosis, gauge overall disease severity, and develop rational treatment plans. This presents an extraordinary measurement challenge—namely, to accurately measure the level of illness severity in a varied group of patients while relying on symptomatic epiphenomenon in lieu of biomarkers of underlying disease activity.
Stratifying patients according to severity is of paramount importance in IBS for at least four reasons. First, in everyday clinical practice, IBS patients are typically trichotomized into “mild, “moderate,” and “severe” groups. This stratification is critical in helping to determine how to tailor therapy to match their level of severity. Second, because there is no consistent objective marker in IBS, clinical trials rely on patient-reported severity outcomes when testing the efficacy of new treatments, which may be only applicable to a subset of patients. Third, the availability of restricted access IBS drugs, such as alosetron and tegaserod, requires that clinicians are capable of selecting the most severe patients when deciding whether to use these drugs. Last, regulatory authorities such as the Food and Drug Administration (FDA) have challenged the validity of existing patient-reported outcomes (e.g., “adequate relief,” “satisfactory relief”), and are increasingly seeking multidimensional outcomes that capture the full disease spectrum. In order to develop new patient-reported measures, investigators must first understand what determines severity in IBS from the perspective of patients.
A recent systematic review hypothesized that IBS severity is a multidimensional concept, which includes health-related quality of life (HRQOL), psychosocial factors, health-care utilization behaviors, and burden of illness. According to this conceptual model, individual symptoms such as abdominal pain are necessary, but not sufficient, to fully embody severity in IBS. A distinction can be made between “symptom severity,” which is measured by items that ask directly about the intensity or bothersomeness of specific IBS symptoms (e.g., pain, bloating, etc.), and “illness severity,” which includes both symptoms and their impact (e.g., interference of daily activities, extraintestinal symptoms, need for health care, etc.). Illness reflects the patient's experience of their disease including behaviors, attributions, and perceptions. It is not known if a patient's perception of their IBS severity is influenced by specific GI symptoms and/or a range of extraintestinal symptoms, which is not captured by the symptom criteria of IBS.
There are several scales that have been validated for the assessment of gastrointestinal symptom severity in IBS. There are currently only two available multidimensional IBS severity instruments that focus on gastrointestinal symptom severity but also measure health-care utilization or impact on daily functioning: (a) the Functional Bowel Disease Severity Index (FBDSI) and (b) the IBS Severity Scale (IBSSS). Although these instruments are useful to allow physicians to risk-stratify patients by severity, they have several limitations, most notably both are physician-derived indices of gastrointestinal symptoms that were not validated from the perspective of patients—the ultimate arbiter of defining severity. In light of these shortcomings, we performed a hypothesis-generating analysis in a large patient cohort to identify clinical predictors of patient self-reported severity in IBS.
Abstract and Introduction
Abstract
Background: Conceptual models suggest that “irritable bowel syndrome (IBS) severity” is a multidimensional outcome that is related to, yet distinct from, health-related quality of life (HRQOL). Existing severity questionnaires are largely based on physician rather than patient-based ratings. Since severity is a patient-centered outcome, it is essential that future instruments are based on patients' self-perceptions of severity. We measured patient-derived predictors of severity in a large cohort of IBS patients.
Methods: We performed a cross-sectional analysis in 755 IBS patients recruited at a university-based center. Subjects completed a bowel symptom questionnaire, SCL-90, and SF-36. The main outcome was patient-assessed “overall severity of gastrointestinal symptoms,” as measured on a 0–20 scale (20 = most severe). We first developed a conceptual model of IBS, and then performed bivariate analyses to identify biopsychosocial predictors of severity. We then entered significant predictors into a multivariable model to measure the independent association of each predictor with severity.
Results: Six factors predicted severity: (a) abdominal pain rating (P < 0.001); (b) belief that “something serious is wrong with body” (P < 0.001); (c) straining with defecation (P= 0.001); (d) myalgias (P= 0.02); (e) urgency with defecation (P= 0.03); and (f) bloating (P= 0.05). Severity correlated highly with HRQOL in bivariate, but not multivariate, analysis.
Conclusion: Patient-derived severity in IBS is related to, yet distinct from, generic HRQOL. IBS severity is predicted by abdominal pain, bloating, straining, urgency, myalgias, and disease-related concern. These symptoms fall along both poles of the “brain-gut axis,” indicating that a full assessment of patient severity must include a balanced biopsychosocial history.
Introduction
Irritable bowel syndrome (IBS) is a disorder of dysregulated brain-gut homeostasis primarily characterized by gastrointestinal symptoms such as abdominal pain, bloating, and altered bowel habits. Yet many patients also may have concurrent extraintestinal symptoms and disease-specific fears and concerns. The heterogeneity of symptom expression suggests that underlying disease mechanisms vary from patient to patient. Experienced clinicians have observed that some IBS patients appear more “brain than gut” in their disease expression, whereas others are more “gut than brain.” The former group may have underlying somatization, catastrophizing, allostatic overload, and maladaptive coping as central mechanisms of disease expression. The latter group may have abnormal motility, imbalanced intestinal flora, or dysregulated intestinal immunity or inflammation as predominant features. Moreover, although the “brain versus gut” dichotomy may have utility in helping clinicians to stratify patients and develop treatment plans, it is more likely that there are not such clearly defined categories, and instead patients have varying combinations of all these proposed mechanisms.
Despite the heterogeneity of disease mechanisms and expressions, the current clinical paradigm is to adhere all patients with the same IBS label, as recommended by the Rome III committee. In the absence of valid and reliable biomarkers to accurately stratify patients within the broader IBS group, clinicians are left interpreting patient-reported symptoms to determine the diagnosis, gauge overall disease severity, and develop rational treatment plans. This presents an extraordinary measurement challenge—namely, to accurately measure the level of illness severity in a varied group of patients while relying on symptomatic epiphenomenon in lieu of biomarkers of underlying disease activity.
Stratifying patients according to severity is of paramount importance in IBS for at least four reasons. First, in everyday clinical practice, IBS patients are typically trichotomized into “mild, “moderate,” and “severe” groups. This stratification is critical in helping to determine how to tailor therapy to match their level of severity. Second, because there is no consistent objective marker in IBS, clinical trials rely on patient-reported severity outcomes when testing the efficacy of new treatments, which may be only applicable to a subset of patients. Third, the availability of restricted access IBS drugs, such as alosetron and tegaserod, requires that clinicians are capable of selecting the most severe patients when deciding whether to use these drugs. Last, regulatory authorities such as the Food and Drug Administration (FDA) have challenged the validity of existing patient-reported outcomes (e.g., “adequate relief,” “satisfactory relief”), and are increasingly seeking multidimensional outcomes that capture the full disease spectrum. In order to develop new patient-reported measures, investigators must first understand what determines severity in IBS from the perspective of patients.
A recent systematic review hypothesized that IBS severity is a multidimensional concept, which includes health-related quality of life (HRQOL), psychosocial factors, health-care utilization behaviors, and burden of illness. According to this conceptual model, individual symptoms such as abdominal pain are necessary, but not sufficient, to fully embody severity in IBS. A distinction can be made between “symptom severity,” which is measured by items that ask directly about the intensity or bothersomeness of specific IBS symptoms (e.g., pain, bloating, etc.), and “illness severity,” which includes both symptoms and their impact (e.g., interference of daily activities, extraintestinal symptoms, need for health care, etc.). Illness reflects the patient's experience of their disease including behaviors, attributions, and perceptions. It is not known if a patient's perception of their IBS severity is influenced by specific GI symptoms and/or a range of extraintestinal symptoms, which is not captured by the symptom criteria of IBS.
There are several scales that have been validated for the assessment of gastrointestinal symptom severity in IBS. There are currently only two available multidimensional IBS severity instruments that focus on gastrointestinal symptom severity but also measure health-care utilization or impact on daily functioning: (a) the Functional Bowel Disease Severity Index (FBDSI) and (b) the IBS Severity Scale (IBSSS). Although these instruments are useful to allow physicians to risk-stratify patients by severity, they have several limitations, most notably both are physician-derived indices of gastrointestinal symptoms that were not validated from the perspective of patients—the ultimate arbiter of defining severity. In light of these shortcomings, we performed a hypothesis-generating analysis in a large patient cohort to identify clinical predictors of patient self-reported severity in IBS.
