Disease perceptions among people with Crohn's disease

Abstract

Background: The relationship between Crohn's disease (CD) patients' perceptions of overall disease course to severity measures based on current symptomatology has not been fully explored. We sought to characterize CD patient perceptions of both overall disease course and current symptomatology based on an objective symptom scale and to explore the relationship between perceptions and current symptoms.

Methods: Patients were screened by telephone and those who met inclusion criteria were invited to complete a full, self-administered online survey.

Results: Respondents (n = 1205) were predominantly female (66%) and Caucasian (92%); the median age was 44 years. Self-perceived overall disease course was described as “mild” in 16%, “moderate” in 50%, and “severe” in 34%; these correlated poorly with objective measures of current symptomatology. Perceived current symptomatology was “mild” in 61%, “moderate” in 29%, and “severe” in 10%. Patients perceived their overall disease course as more severe than that reflected by current symptomatology. Among 61% who had “mild” disease based on 30-day symptoms, only 16% rated themselves as having a mild disease course overall. Similar results among those in the “moderate” and “severe” overall disease categories indicated poor congruence between perceived overall disease course and measures of current disease symptomatology.

Conclusions: Perceptions of overall disease severity may not correlate with disease activity measures based on current symptomatology. Patients rely on physicians to guide treatment choices; thus, a more complete appreciation of patients' disease perceptions that includes both overall disease course and current symptomatology may help inform treatment decisions, and could potentially improve patient care.

(Inflamm Bowel Dis 2008)

The treatment of Crohn's disease (CD) has changed dramatically in recent years as new therapies have been developed and indications for treatment have expanded. While offering significant advances in efficacy, especially for patients with refractory CD, these treatments may confer significant short- and long-term risks. As CD remains incurable, treatment principles highlight the balance of efficacy and safety.1 Evidence-based guidelines derived from population-based data may be difficult to apply to the individual patient with his or her unique clinical presentation and preferences.

Although an increasing body of inflammatory bowel disease literature has focused on the concept of “quality of life,” a subjective measure of patients' perception of health encompassing not only physical but emotional and social concerns, little is known about how patients with CD perceive the severity of their overall disease course.2–5 How this perception correlates with disease measures based on current symptomatology, and how patients view their role in the treatment decision-making process, is equally unexplored. Disease severity measures often incorporate information available at a single point in time. Such measures may not accurately assess the overall severity of CD, given its relapsing and remitting nature.

Graff et al6 highlighted this problem in their study of more than 380 patients with both ulcerative colitis (UC) and CD—they noted that disease-related impact on quality of life remained even when the disease was inactive. Sole reliance on physician assessment of disease at any specific timepoint may underestimate disease burden. It may also undervalue the potential benefit of ongoing treatment from the patient's perspective, especially as recent data are conflicting about the knowledge that patients with CD have of treatment-related risks or their willingness to assume such risks to potentially improve their health.7, 8

We sought to characterize CD patients' views of disease severity based on overall course, and the concordance of these perceptions with a measure based on disease symptomatology within the past 30 days. We also explored patient views of treatment decision making and their correlation with both overall disease course and current symptomatology.

MATERIALS AND METHODS

Survey Conduct and Recruitment

The authors at academic institutions (S.V.K., E.V.L., and M.C.D.) were notified either verbally or in writing by their respective Institutional Review Boards (IRB) that this study was exempt from IRB approval. The survey was administered by a third party, healthcare-focused market research company. Data from IMS Health and Wolter Kluwers were analyzed to identify physicians with high-volume inflammatory bowel disease practices based on their prescribing of “Crohn's disease medications” (e.g., 5-aminosalicylates [5-ASA], sulfasalazine, corticosteroids, immunosuppressants), as well as their use of infliximab. These physicians were then contacted by the third-party research agency to apprise them of the study; gastroenterologists who expressed interest were further screened to identify those who saw at least 10 patients with CD each month. In all, 377 screened physicians were paid $150 to complete an ≈20-minute survey. Each participating physician also received 20 patient recruitment cards; however, photocopied or verbal invitations were also accepted. The physicians received $50 for each patient they recruited to complete a survey that consisted of 64 questions requiring an average of 20 minutes to complete. Overall, 324 (86%) physicians had patients that chose to participate. It was left to the discretion of the individual physicians to approach patients that were appropriate for potential inclusion. The physician was asked to recruit those patients from the practice with a definitive diagnosis of CD based on standard radiographic, endoscopic, and histologic criteria.

Survey participation was targeted to 1200 patients, with 50% to be between the ages of 18 and 39 years. The survey was performed during January and February 2006. Patients were initially screened by telephone, and those that met inclusion criteria were invited to complete the full, self-administered survey online. In order to recruit a diverse sample of patients, there were few inclusion and exclusion criteria. Inclusion criteria included a physician-based diagnosis of CD and the ability to complete an Internet-based survey. Patients were excluded if they were younger than 18 years of age, had not been definitively diagnosed with CD, had disease duration of less than 2 years, or were unable to complete an Internet-based survey. Additionally, patients were screened to meet target gender, age-range, and disease severity quotas. The latter criterion was based on self-assessment of overall disease course, regardless of whether the respondent was currently symptom-free (on or off medication). Each patient that completed the survey received a $35 honorarium.

To ensure patients' privacy, no individually identifiable data were retained and only aggregate data were available to the sponsor and authors. The total response rate was estimated to be ≈16%.

Survey Components

Survey components included information about basic demographics, overall disease course, current symptoms within 30 days, patients' treatment decision-making preferences, physician–patient relationships, and sources of treatment information. Self-reported disease-specific information focused on overall disease course and current symptomatology. First, patients classified their perceived overall disease course, separate from any current symptoms, as mild, moderate, or severe (Appendix). Next, patients responded to a general question about current symptoms (Appendix) and provided a more detailed assessment of current symptomatology based on symptoms over the previous 30 days. For this latter assessment, participants reviewed a chart containing specific findings, many of which were similar to those of the Crohn's Disease Activity Index (CDAI) (Table 1), and characterized themselves as having “mild,” “moderate,” or “severe” disease. Thus, participants had both a subjective measure of overall disease course and an objective assessment of current (30-day) disease symptomatology. Subsequent questions elicited more specific details about the frequency of specific symptoms over the previous 30-day period, including number of episodes of cramping or sharp pain in an average week, number of daily bowel movements, and number of days in an average week that diarrhea occurred (Appendix) Other information that participants provided included: current medications (chosen from a list with an option for free text), current symptoms, and surgical history.

Table 1. —Current Symptomatology (Last 30 Days): patients reviewed this table to characterize their recent disease activity.

	Mild	Moderate	Severe
Categorization based on American College of Gastroenterology Guidelines1
Pain	Intermittent cramping	Frequent cramping	Severe, frequent cramping or colicky pain Dull, aching pain
Diarrhea	<4 movements/day	4–6 movements/day	>6 movements/day Liquid stools
Blood in Stool	Rare	Frequent	Frequent, gross bleeding Massive bleeding in a minority of cases
Fever	Only in case of aggravated symptoms	Frequent low-grade	Moderate- to high-grade High spiking fever
Loss of Appetite	Common	Common	Common
Weight Loss	Minimal	Moderate	Significant
Anemia- need iron supplements	Mild	Mild	Moderate
Difficulty maintaining weight	Rare	Common	Common

Medical decision making was explored through another series of questions. These ranged from specifically how the respondent perceived that his or her physician made CD-related treatment decisions, as well as general questions about how the respondent thought such decisions should be made. Respondents who were currently receiving or had previously received anti-TNF-α therapy were also asked whether they or their doctor had initiated the discussion of that treatment and, if no longer on such therapy, why treatment was discontinued.

RESULTS

Demographics

In total, 1205 people with CD, representing the entire United States, participated in this survey. Women comprised 66% of the respondents. The vast majority (92%) of patients were Caucasian, 3.3% were African-American, and the remainder were comprised of other racial groups. The median age was 44 years (mean, 42.9; range, 18–70 years). Respondents were generally well-educated—over 23% graduated college and over 11% had postgraduate degrees. The median number of gastroenterologists that respondents had seen was 2 (mean, 2.7; range, 1–30), although this number was higher among those with more severe disease.

Measures of Overall Disease Course and Current Disease Severity

Among the 1205 respondents, overall subjective disease course severity was described as “mild” in 193 (16%), “moderate” in 605 (50%), and “severe” in 407 (34%). Current symptomatology, however, was reported as “mild” in 61%, “moderate” in 29%, and “severe” in 10% (Fig. 1). Participants perceived their overall disease activity as more severe than that reflected by measures of current symptoms. Of the 16% of participants who perceived their overall disease course as “mild,” 96% characterized their current symptoms to be “mild”; 4%, “moderate”; and none, “severe.” Among the 50% of patients who perceived their overall disease course as “moderate,” 65% reported current symptoms as “mild,” and only 35% and 3% reported current symptoms as “moderate” and “severe,” respectively. Among the 34% of patients who perceived their overall disease course as “severe,” 42% and 32% evaluated their current symptomatology as “mild” and “moderate,” while only 26% of these characterized current symptoms as “severe.” These data indicate poor congruence of patient overall disease ratings and measures of disease severity based on symptoms over the past 30 days. It is important to note that even patients with self-described mild disease had significant symptoms, noting, on average, nearly 2 days each week with cramping abdominal pain, and more than 2 days each week with diarrhea.

Figure 1. Concordance of overall subjective disease severity and current symptomatology.

Medication Use

A high proportion of participants reported current use of 5-ASA products and/or corticosteroids (Table 2). When medication use was evaluated based on overall subjective disease severity, 4% of those with “mild” and 11% of those with “moderate” disease reported corticosteroid use continuously for more than 2 months. Immunosuppressant use was reported in 12% of “mild,” 28% of “moderate,” and 34% of those with “severe” disease. Biologic therapy was currently being used by 8% and previously used by 6% of those with “mild” overall severity. Among those with “severe” overall subjective severity, 34% and 22% were current and former biologic therapy users, respectively. Nearly one-half of those with severe overall subjective severity (44%) reported no current or previous biologic therapy use. Sixty-two percent of patients who perceived their overall disease course as “severe” reported 1 or more surgeries for CD. Mild and moderate patients report 21% and 40% surgery rates for their CD, respectively.

Table 2. —Current Medication Use by Overall Subjective Disease Course

Medication	Mild N = 193	Moderate N = 605	Severe N= 407
A: p value compared to mild < 0.05 * Balsalazide sodium, olsalazine sodium, mesalamine, sulfasalazine B: p value compared to moderate < 0.05 ** azathioprine, 6-mercaptopurine, methotrexate C: p value compared to severe < 0.05 # corticosteroids taken continuously for > 2 months ## corticosteroids taken for < 2 months
Current 5-Aminosalicylates*	43 %	50% (C)	43 %
Current; immunosuppressives**	12 %	28 % (A)	34 % (A,B)
Current Long-term corticosteroids#	4 %	11 % (A)	16 % (A,B)
Current short-term corticosteroids##	1 %	7 % (A)	8 % (A)
Current Biologics***	8 %	23 % (A)	34 (A,B)
Former Biologics	6 %	19 % (A)	22 % (A)
Biologics Naïve	86 % (B,C)	58 % (C)	44 %

Treatment Decision Making

Perceived overall severity of disease course also played a role in patient perceptions of their role in treatment decisions. When asked to characterize their involvement in treatment decisions, respondents that perceived their overall disease course as moderate or severe reported a greater degree of involvement in treatment decisions and less reliance on their physician. For patients that perceived their overall disease course as severe, 68% reported that decision making was a partnership or that they preferred to “take the lead” based on their gastroenterologist's opinion, compared with 32% who described that their doctor made decisions or led decision making. Among those with overall disease course described as moderate or mild, slightly fewer described active involvement in treatment decisions (63% and 56%, respectively).

Current symptomatology appeared to be a more significant indicator of willingness to try new therapies than overall disease course. Among those with severe current symptomatology, 67.2% indicated they were “very willing” to try new treatments, a designation defined by a response of 6 or 7 on a 7-point scale. This figure was 50.6% for those with moderate current symptoms. Only 31.4% of patients with mild current symptoms indicated that they were “very willing” to try new treatments.

Biologic Therapy

Among the survey participants who were currently using or had previously used biologic therapy with an anti-TNF-α agent (n = 511), ≈19% reported that they, not their physician, had initiated the discussion. In the subsets of participants who had previously but were not currently using anti-TNF-α therapy, the reasons for treatment discontinuation included: loss of efficacy (17%), side effects (22%), cost (11%), and “physician stopped” the therapy (23%); survey respondents could cite more than 1 reason (Table 3). The specific reasons for physician discontinuation of the biologic agent were not assessed in this survey.

Table 3. —Reasons for Discontinuation of Biologic Therapy

Overall Rating of Disease	Mild N = 11	Moderate N = 116	Severe N = 91	Total N = 218
Note: Patients could check more than one reason. No p values < 0.05
Physician stopped	46%	22%	23%	23%
Loss of Efficacy	9%	20%	14%	17%
Cost Issues	9%	10%	13%	11%
Side Effects	9%	24%	21%	22%

DISCUSSION

Little is known about how patients with CD or their doctors make treatment decisions. It is likely that an important factor when weighing the risks and benefits of treatment is the perceived burden of disease. Our survey data indicate that patient perceptions of overall disease severity do not necessarily correlate with how a patient perceives their current symptoms. The discordance between measures of current symptomatology and patient perceptions of overall disease activity may be related to the relapsing-remitting nature of the disease and potential recall bias, and highlights the potential limitations of widely used severity measures that are based solely on current disease symptomatology. None of our current methods of estimating disease severity incorporated the patient's short- or long-term disease history. Our data suggest that even among patients with apparently mild disease, patients have significant symptom burden.

While patients with moderate or severe disease reported a higher degree of involvement in treatment decision making, over one-third appeared to rely significantly on their physicians to make treatment decisions for them. Potential discordance between physician perception (presumably based on short-term measures of symptomatology) and patient perception of disease burden may significantly impact treatment decisions both short- and long-term.

Patients also vary in their willingness to incur risks in order to potentially benefit from new treatments. Sands et al7 recently reported that among survey respondents with moderate to severe CD, patients were willing to incur risks of serious outcomes, such as lymphoma, for potential benefit at rates greater than those their physicians were willing to assume. It is not clear what drives this difference: lower estimation of potential benefit and greater estimation of adverse event risk by physicians or greater assessment of potential benefits and underestimation of adverse events by patients.8

Interestingly, among patients exposed to biologic therapy factors besides efficacy, side effects, and costs appeared to drive treatment discontinuation in some cases. Further exploration to clarify these factors may illuminate important pieces of the treatment decision-making process and may gain greater importance as the role for biologic therapy within the CD treatment paradigm evolves.

Our survey was quantitative and descriptive. Although it highlighted areas for further study, it had some important limitations. Our respondents had to have access to and comfort with using the Internet to participate in this self-administered survey. Our respondents were primarily Caucasian, further limiting the generalizability of this survey. Patients had more severe self-reported disease activity, which may reflect the demographics of the practices of the gastroenterologists who recruited them to participate, or may reflect a subset of patients who are more highly motivated to participate in a survey. Balancing these concerns is the large number of survey respondents from multiple geographic areas and the fact that symptom severity was not an exclusionary criterion. Another limitation is the lack of information regarding those patients who declined to participate or who met exclusionary criteria. Whether those patients who declined are more or less ill than those who did may bias the conclusions. Understanding the motivation of patients to participate in such surveys in future research will help to clarify this issue.

Treatment decisions in CD may be further complicated by changes in the treatment paradigm. In the past, treatment for CD consisted of “step-up” or sequential treatment targeted to the severity of patient symptoms. Recent data, however, suggest that a “top-down” approach using biologic therapies earlier might slow disease progression and modify disease course.9 In addition, for patients with steroid refractory or fistulizing disease, biologics appear relatively more effective is controlling disease than traditional nonbiologic therapies. Among patients with fistulizing disease the use of maintenance therapy with infliximab was associated with decreased hospitalizations, surgeries, and decreased use of other procedures.10

As patients continue to rely on physicians to guide treatment choices, methods to facilitate a more detailed understanding of disease burden may help physicians and patients make more informed treatment choices to minimize disease burden and improve long-term outcomes.

Acknowledgements

The authors thank Carol R. Regueiro, MD, MSc, for assistance in the preparation of this article.

APPENDIX

1) Would you generally describe your Crohn's disease as mild, moderate, or severe? (Please note, we are interested in the severity of your Crohn's overall, even though currently your symptoms may be controlled by medication or you may be in a remission or symptom-free state.)

 (1) Mild

 (2) Moderate

 (3) Severe

2) Would you describe your current Crohn's symptoms over the last month as high activity, low activity, or remission (symptom free)? (Select one response)

 (1) High activity

 (2) Low activity

 (3) Remission (symptom free)

3) Still thinking about the last 30 days:

 (1) How many days in an average week do you have cramping pain?  ______ # of days

 (2) Do you ever have sharp pain?  ______ Yes/No

 (3) How many bowel movements do you have each day?  ______ # of bowel movements

 (4) How many days in an average week do you have diarrhea?  ______ # of days