Dig Dis Sci DOI 10.1007/s10620-014-3141-3
ORIGINAL ARTICLE
Racial Differences in Disease Activity and Quality of Life in Patients with Crohn’s Disease Leyla J. Ghazi • Alison D. Lydecker • Seema A. Patil • Ankur Rustgi • Raymond K. Cross Mark H. Flasar
•
Received: 19 November 2013 / Accepted: 26 March 2014 Ó Springer Science+Business Media New York 2014
Abstract Background The existing literature on racial differences in Crohn’s disease (CD) activity and quality of life (QOL) is limited and extrapolated from surrogate measures. Aim The aim of our study was to compare objective markers of disease activity and QOL over time by race. Study A clinical data repository of inflammatory bowel disease (IBD) patients at University of Maryland, Baltimore IBD Program, was used. CD patients from 2004 to 2009 were included if they had greater than or equal to two clinic visits with disease activity and QOL scores during the study period. Differences in disease activity and QOL were compared by race over time. Results A total of 296 patients with CD met inclusion criteria; of these, 19 % (56/296) were African Americans (AA) and 81 % (240/296) were Caucasian. Baseline disease activity and QOL scores did not differ by race (p [ 0.05). Caucasians had a steady decline in disease activity and increase in QOL. AA experienced a similar pattern of change in disease activity and QOL scores over time; however, the declines were not statistically significant between groups. At each time point post-baseline, L. J. Ghazi (&) S. A. Patil A. Rustgi R. K. Cross M. H. Flasar Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 100 North Greene Street, Lower Level, Baltimore, MD 21201, USA e-mail: [email protected] L. J. Ghazi S. A. Patil M. H. Flasar Veterans Affairs, Maryland Heath Care System, Baltimore, MD, USA A. D. Lydecker Department of Epidemiology and Biostatistics, University of Maryland School of Medicine, Baltimore, MD, USA
disease activity and QOL scores were similar between races. Conclusion We found that Caucasian and AA patients with CD had similar disease activity and QOL scores at initial presentation and over time. Thus, AA do not represent a more severe subgroup of CD patients to treat. These findings have important implications for clinicians that care for patients with CD. Keywords Healthcare disparities Inflammatory bowel disease Minority health Crohn’s disease
Introduction Inflammatory bowel disease (IBD) is a chronic inflammatory condition that targets the gastrointestinal tract, with higher incidence and prevalence rates reported in Caucasians compared to African Americans (AA). Ulcerative colitis (UC) and Crohn’s disease (CD), the two main subtypes, are estimated to affect over 1 million patients in the USA [1]. Despite the high prevalence in the USA, data regarding racial differences in disease phenotype, severity, surgical rates, extra intestinal manifestations, and medication use are scarce. Our current understanding of IBD epidemiology is based upon studies conducted in primarily Caucasian populations in North America and Europe, such as Olmsted County, MN, Manitoba, Canada, and Scandinavia [1]; studies evaluating IBD natural history, medication response, and surgical outcomes have also been conducted in [90 % Caucasian populations [2–5]. Since 2005, there has been a rise in published studies to elucidate racial differences between Caucasians and AA. Among studies, 11.2–37 % of patients were AA [6–12].
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Previous studies on differences in disease severity have not used validated clinical indices of disease activity. Surrogate markers of disease severity such as use of steroids, hospitalization, and surgery have revealed conflicting results. Two studies found no differences in disease severity by race [7, 12]; however, differences in health care utilization practices and impact on quality of life (QOL) have been observed [12]. A review of hospital discharges of IBD patients residing in San Francisco, CA, revealed an overall trend toward increasing hospitalizations in minorities from 1994 to 2006, including AA [11]. Though AA appear to have overall lower rates of bowel resection compared to Caucasians, the latter have experienced a 50 % decline in bowel resections from 1998 to 2003, a trend that was not observed in AA [13]. Deveaux et al. [14] also reported similar mean operations and frequency of surgery by race. CD behavior may also serve as a surrogate marker of disease severity. A review of IBD database from University of Chicago in 1971 demonstrated a threefold increase in the risk of perianal complications in AA patients compared to Caucasians [15]. Higher rates of fistulizing CD have been found in adult AA patients from the Jewish Hospital in St Louis, MO, and in pediatric AA patients from Georgia [16, 17]. Larger series have reported rates of perianal disease in AA patients that are equal to those of Caucasians [14, 18]. There are no data from prospective cohorts and clinical trials about differences in disease activity and QOL using validated indices of disease activity. The objective of this study was to assess for racial differences in disease activity and QOL over time among CD patients in a tertiary referral practice.
Materials and Methods Design We performed a retrospective cohort study of adult outpatients with CD evaluated at the University of Maryland, Baltimore IBD Program between July 1, 2004 and December 31, 2009. Identification of Subjects Confirmation of the diagnosis of CD was made following review of the patient’s medical records using standard clinical, radiologic, pathologic, and endoscopic criteria [19]. Patients who had indeterminate colitis or ulcerative colitis were excluded. Race was determined by patient report as Caucasian (non-Hispanic) or African American. Patients at the University of Maryland, Baltimore, respond to a single question regarding race on a Patient Health
123
Questionnaire. This response is scanned into an IRBapproved clinical data repository. The clinical data repository is a prospectively collected data repository that includes information on demographics, disease duration, IBD phenotype, extraintestinal manifestations of disease, medication exposure, hospitalizations, and surgeries. CD disease activity is assessed at each visit using the Harvey Bradshaw Index (HBI). Disease-specific QOL is measured at each visit using the Short Form Inflammatory Bowel Disease Questionnaire (SIBDQ) [20]. We identified Caucasian and AA CD patients who had greater than or equal to two valid scores for the HBI (C0) and SIBDQ (10–70) at two consecutive clinic visits. Data Analysis Baseline differences in participant characteristics by race were assessed using t tests for continuous variables and chi-square or Fisher’s exact test as appropriate for categorical variables. Clinic visits occurred as needed for proper clinical care, not on a set study schedule, and were therefore grouped into visit windows in order to make comparisons. The first visit during the study time frame was considered the baseline visit (Day 0). Visit windows were calculated based on number of days since the first visit that occurred in the study time frame (Day 0, Day 1–90, 91–180, 181–270, 271–360, 361–540, 541–720, 721–900, Day 901–1080). If multiple clinic visits occurred during a visit window, the disease activity and QOL values were used for the last visit in the window. If a patient was missing values for a given visit window, and had values for a subsequent visit window, the values from the most recent visit window were carried forward. Values were not carried forward if a patient did not have any subsequent visits. Preliminary graphs indicated that the relationship between disease activity/QOL and time changed between the first 180 days and the remainder of the study period. A spline was added after the Day 90–180 visit window to allow for this modification of the relationship. Two analyses were conducted separately. First, the relationship between disease activity and race over time was examined. Secondly, the relationship between QOL and race over time was examined. In each case, the relationship was assessed using a generalized estimating equation regression with robust variance estimation to correct for correlations caused by multiple clinic visits for each patient. Regressions included race, time, a spline at 180 days, the interaction between race and time, and the outcome variable of interest. All statistical tests were two sided. p values \0.05 were considered statistically significant. All statistical analyses were conducted with Stata 10 software (Stata Corporation, College Station, TX).
Dig Dis Sci Table 1 Baseline characteristics of patients with Crohn’s disease evaluated at the University of Maryland, Baltimore IBD Program between July 1, 2004 and December 31, 2009 (n = 296)
Characteristic
Total (n = 296)
White (n = 240)
African American (n = 56)
Male
116
99 (41)
17 (30)
Female
p value*
n (%) or mean ± SD Gender
0.13 180
141 (59)
39 (70)
Age at diagnosis (years)
28 ± 14
29 ± 14
26 ± 14
0.15
Current age (years)
40 ± 14
41 ± 14
40 ± 15
0.67
Never
163 (55)
128 (53)
35 (63)
Former
65 (22)
54 (23)
11 (20)
Current
68 (23)
58 (24)
10 (18)
99
84 (38)
15 (31)
Smoking status
0.44
Phenotype Location L1, ileal
0.46
L2, colonic
49
44 (20)
5 (12)
L3, ileocolonic
114
91 (42)
23 (55)
43
36 (15)
7 (15)
Location modifier L4, isolated upper disease
0.83
Behavior
0.08
B1, non-stricturing
89
79 (33)
10 (18)
B2, stricturing
108
85 (36)
23 (42)
B3, Penetrating
95
73 (31)
22 (40)
80
60 (25)
20 (36)
Behavior modifier P, Perianal disease
0.13
Presence of any EIM (except gallstones, arthralgias)
0.46
Yes
86
72 (30)
14 (25)
No
210
168 (70)
42 (75)
Prednisone
249
194 (80)
55 (20)
0.96
Immunomodulatorsa
218
173 (79)
45 (21)
0.33
Biologics
196
152 (78)
44 (22)
0.81
Infliximab
178
135 (76)
43 (24)
0.28
Adalimumab
81
64 (79)
17 (21)
0.79
Certolizumab pegol
9
5 (56)
4 (44)
0.09
Natalizumab
1
1 (100)
0 (0)
0.59
Medication exposure
a
Immunomodulators include 6-mercaptopurine (mp), azathioprine, and/or methotrexate (MTX) * p values from chi-square test, Fisher’s exact test, or t test, as appropriate
Results Participant Demographics Two hundred ninety-six patients with CD were identified who met the inclusion criteria. AA comprised 19 % (56/ 296) of the cohort. Detailed characteristics of all CD patients are listed in Table 1. There was no difference by race in gender, age at diagnosis, current age, smoking status, disease location, or the presence of extraintestinal manifestations of disease (excluding gallstones and arthralgias). There were no differences in medication exposure between races. A higher proportion of AA had penetrating
and stricturing disease behavior and perianal involvement compared to Caucasians; however, the differences were not statistically significant (Table 1). Differences in Disease Activity Between Caucasians and AA At baseline, Caucasians had a mean HBI score of 6.3 ± 5.2 (compared to 7.0 ± 5.6 for AA) (p = 0.43). In the first 180 days, the HBI score of Caucasians decreased 2.1 points and that of AA decreased 1.6 points (p \ 0.01 and p = 0.01, respectively, compared to baseline) (p = 0.44). The difference in the average decrease in HBI score in the
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Fig. 1 HBI scores over time in Caucasians and AA with Crohn’s disease
Fig. 2 SIBDQ scores over time in Caucasians and AA with Crohn’s disease
first 180 days is not statistically significant by race. After the first 180 days, the HBI score of Caucasians decrease 0.3 points with each increase of 180 days (p \ 0.01), and the change from the first 180 days is statistically significant (p \ 0.01). Similarly, the HBI score of AA decreases 0.2 with each visit window (p = 0.54). The relationship between the HBI score in the first 180 days and remaining time in the study is not different by race (p = 0.64). The data are descriptively depicted in Fig. 1.
time by race in individuals with CD. Within 6 months of initiating care at a tertiary referral center, we found that both AA and Caucasians had significantly reduced disease activity and improved QOL. In subsequent time periods, these trends persisted in both AA and Caucasians; however, the results were significant only in Caucasian patients. No differences in disease activity or QOL scores were noted by race at any time point post-baseline. To our knowledge, this study is the first to evaluate for racial differences in disease activity and QOL over time using validated disease activity and QOL indices. Previous literature has published conflicting results regarding differences in disease severity by race using surrogate measures of activity/severity such as disease behavior, steroid use, hospitalizations, and surgery. In contrast to our study, prior studies have reported differences in disease behavior by race. In a large North American cohort, a higher rate of perforating disease behavior was found in Caucasians compared to AA (30 vs. 19 %). Nguyen et al. [10] found that AA had a higher rate of obstructing disease behavior compared to Caucasians (38 vs. 24 %). Conversely, others have not detected differences in disease behavior. In a cohort of patients presenting for surgical procedures, Deveaux et al. [14] found similar rates of fistulizing complications. Kugathasan et al. [21] found similar phenotypic features of CD among AA and Hispanic children compared with white children. Moreover, prior studies have reported a greater prevalence of perianal involvement in AA [10, 12, 15]. Although the rate of perianal involvement was greater in AA in our study, the difference was not significant to reflect meaningful comparisons. The use of differing criterion to describe perianal CD may explain the differences among studies, as other studies have utilized a broader definition of perianal involvement. Previous literature has published conflicting results regarding differences in disease severity by race using
Difference in Disease-Specific Quality of Life Between Caucasians and AA At baseline, Caucasians had a mean SIBDQ score of 43.2 ± 14, compared to 40.8 ± 15 for AA (p = 0.32). In the first 180 days, the SIBDQ scores of Caucasians increase by 6.1 points (p \ 0.01 compared to baseline). Similarly, the SIBDQ score of AA increases by 6.6 points in the first 180 days (p \ 0.01 compared to baseline). The difference in the average increase in SIBDQ score in the first 180 days was not different by race (p = 0.80). After the first 180 days, the SIBDQ score of Caucasians increases, on average, 1.4 points with each increase of 180 days (p \ 0.01). Similarly, the SIBDQ score of AA increases, on average, 1.2 points with each increase of 180 days (p \ 0.01). The change in the average amount of SIBDQ increase between the first 180 days and the remaining time in the study is statistically significant (p \ 0.01) for both Caucasians and AA. This relationship was not statistically significantly different by race (p = 0.76). The data are descriptively depicted in Fig. 2.
Discussion This retrospective study of prospectively collected data showed no differences in the disease activity or QOL over
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other measures of disease activity such extraintestinal manifestations, hospitalizations, and surgery. A large multicenter analysis found a lower rate of surgery among AA compared to Caucasians; this racial difference persisted after adjustment for disease behavior and location [10]. Others have identified similar [7, 12] or increased rates of surgery when comparing races [17]. Nguyen et al. [10] also found obvious differences in the distribution of EIM among IBD patients, such as a four-fold greater prevalence of uveitis, and higher rates of sacroiliitis in AA compared to Caucasians. We did not compare differences in surgical rates by race in this study. We did evaluate EIM by race but found no racial differences in the distribution of EIM. However, our study is limited by significantly smaller number of participants. A systematic review of previously published literature found that the prevalence of joint problems, the most common EIM in both populations, was similar by race [22]. A subsequent systematic review of six published studies identified few differences between Caucasians and AA, namely a higher rate of skin and joint manifestations in AA [23]. Differences in treatment have been proposed as a possible etiology for differing severity of disease. Some single center studies have found no overall differences in medical treatment between Caucasians and AA [6, 11], while others found trends toward lower odds of treatment with infliximab (IFX) and immunomodulators [6-mercaptopurine(6MP)/azathioprine (AZA)] [8]. Steroid use did not seem to differ between races in these studies suggesting comparable disease severity. Our study found no differences in medication exposure at a single time point by race. An evaluation of medication exposure at differing time points may have been helpful in determining whether there are parallel changes in medication exposure as QOL and disease activity improve. Our study has several important strengths. The University of Maryland, Baltimore IBD program, has a higher proportion of AA patients with IBD and CD compared to other centers. We used validated indices rather than surrogate markers of disease activity to assess disease activity over time. Though the study design is retrospective, we used prospectively collected data regarding disease activity and QOL. Our study had several limitations. First, despite the comparatively high proportion of AA patients with CD, we still had a small absolute number of patients for analysis. This may limit the ability to detect small to moderate differences in disease activity or QOL by race. Although our length of follow-up was reasonable, on average, we do not have more than 3 years of follow-up data to identify later changes in disease activity. Further, because our cohort study began at the time of initial visit to our program, we cannot evaluate differences in disease activity at various time points in the disease process (early vs. late
activity). Lastly, even though we used validated disease activity indices, symptom-based activity indices themselves have limitations. It is possible that higher disease activity scores do not actually represent disease activity but relate to superimposed irritable bowel syndrome, antecedent viral syndromes, or other causes of elevated activity scores. Although possible, it is unlikely that there are significant differences in symptom-based reporting of CD symptoms by race. In summary, we found that Caucasian and AA patients with CD had similar disease activity and QOL scores at presentation to a referral center. Likewise, disease activity and QOL improved in both racial groups over time. These findings have important implications for clinicians that care for patients with IBD. First, we cannot confirm differences in disease activity between Caucasians and AA with CD. Thus, AA do not represent a more or less severe subgroup of CD patients to treat. Second, it does not appear that racial differences in previously utilized surrogate markers of disease behavior, such as penetrating phenotype, perianal complications, or EIMs exist in our cohort of patients, thereby lending further support to the notion that AA are not a more severe subgroup of CD patients. Further research is needed to identify reasons for disparities in treatment such as patient or provider bias or access to care issues. Conflict of interest
None.
References 1. Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology. 2004;126:1504–1517. 2. Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132: 52–65. 3. Hanauer SB, Feagan BG, Lichtenstein GR, et al. ACCENT I Study Group. Maintenance infliximab for Crohn’s disease: the ACCENT I randomized trial. Lancet 2002;359:1541–1549. 4. Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med. 2007;357: 228–238. 5. Vind I, Riis L, Jess T, et al, the DCCD Study Group. Increasing incidences of inflammatory bowel disease and decreasing surgery rates in Copenhagen City and County, 2003–2005: a populationbased study from the Danish Crohn colitis database. Am J Gastroenterol 2006;101:1274–1282. 6. Basu S, Lopez I, Kulkarni A, et al. Impact of race and ethnicity on inflammatory bowel disease. Am J Gastroenterol. 2005;100: 2254–2261. 7. Cross RK, Jung C, Wasan S, et al. Racial differences in disease phenotype in patients with Crohn’s disease. Inflamm Bowel Dis. 2006;12:192–198. 8. Flasar MH, Johnson T, Roghmann M, et al. Disparities in the use of immunomodulators and biologics for the treatment of inflammatory bowel disease: a retrospective cohort study. Inflamm Bowel Dis. 2008;14:13–19.
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Dig Dis Sci 9. Flasar MH, Quezada S, Bijpuria P, et al. Racial differences in disease extent and severity in patients with ulcerative colitis: a retrospective cohort study. Dig Dis Sci. 2008;53:2754–2760. 10. Nguyen GC, Torres EA, Regueiro M, et al. Inflammatory bowel disease characteristics among African Americans, Hispanics, and Non-Hispanic Whites: characterization of a large North American cohort. Am J Gastroenterol. 2006;101:1012–1023. 11. Sewell JL, Yee HF, Inadomi JM. Hospitalizations are increasing among minority patients with Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis. 2010;16:204–207. 12. Straus WL, Eisen GM, Sandler RS, et al. Crohn’s disease: does race matter? Am J Gastroenterol. 2000;95:479–483. 13. Nguyen GC, Bayless TM, Powe NR, et al. Race and health insurance are predictors of hospitalized Crohn’s disease patients in undergoing bowel resection. Inflamm Bowel Dis. 2007;13: 1408–1416. 14. Deveaux PG, Kimberling J, Galandiuk S, et al. Crohn’s disease: presentation and severity compared between black patients and white patients. Dis Colon Rectum. 2005;48:1404–1409. 15. Samuels AD, Weese JL, Berman PM, et al. An epidemiologic and demographic study of inflammatory bowel disease in black patients. Am J Dig Dis. 1974;19:156–160. 16. Ogunbi SO, Ransom JA, Sullivan K, et al. Inflammatory bowel disease in African-American children living in Georgia. J Pediatr. 1998;133:103–107.
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17. Goldman CD, Kodner IJ, Fry RD, et al. Clinical and operative experience with non-Caucasian patients with Crohn’s disease. Dis Colon Rectum. 1986;29:317–321. 18. Satsangi J, Silverberg MS, Vermeire S. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55:749–753. 19. Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2–6. 20. Irvine E, Zhou Q, Thompson AK. The Short Inflammatory Bowel Disease Questionnaire: a quality of life instrument for community physicians managing inflammatory bowel disease. CCRPT Investigators, Canadian Crohn’s Relapse Prevention Trial. Am J Gastroenterol. 1996;91:1571–1578. 21. Kugathasan S, Loizides A, Babusukumar U, et al. Comparative phenotypic and CARD15 mutational analysis among African American, Hispanic, and White children with Crohn’s disease. Inflamm Bowel Dis. 2005;11:631–638. 22. Mahid SS, Aaron MM, Gholson RD, et al. Inflammatory bowel disease and African Americans: a systematic review. Inflamm Bowel Dis. 2008;14:960–967. 23. Hou JK, El-Serag H, Thirumurthi S. Distribution and manifestations of inflammatory bowel disease in Asians, Hispanics, and African Americans: a systematic review. Am J Gastroenterol. 2009;104:2100–2109.
ORIGINAL ARTICLE
Racial Differences in Disease Activity and Quality of Life in Patients with Crohn’s Disease Leyla J. Ghazi • Alison D. Lydecker • Seema A. Patil • Ankur Rustgi • Raymond K. Cross Mark H. Flasar
•
Received: 19 November 2013 / Accepted: 26 March 2014 Ó Springer Science+Business Media New York 2014
Abstract Background The existing literature on racial differences in Crohn’s disease (CD) activity and quality of life (QOL) is limited and extrapolated from surrogate measures. Aim The aim of our study was to compare objective markers of disease activity and QOL over time by race. Study A clinical data repository of inflammatory bowel disease (IBD) patients at University of Maryland, Baltimore IBD Program, was used. CD patients from 2004 to 2009 were included if they had greater than or equal to two clinic visits with disease activity and QOL scores during the study period. Differences in disease activity and QOL were compared by race over time. Results A total of 296 patients with CD met inclusion criteria; of these, 19 % (56/296) were African Americans (AA) and 81 % (240/296) were Caucasian. Baseline disease activity and QOL scores did not differ by race (p [ 0.05). Caucasians had a steady decline in disease activity and increase in QOL. AA experienced a similar pattern of change in disease activity and QOL scores over time; however, the declines were not statistically significant between groups. At each time point post-baseline, L. J. Ghazi (&) S. A. Patil A. Rustgi R. K. Cross M. H. Flasar Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 100 North Greene Street, Lower Level, Baltimore, MD 21201, USA e-mail: [email protected] L. J. Ghazi S. A. Patil M. H. Flasar Veterans Affairs, Maryland Heath Care System, Baltimore, MD, USA A. D. Lydecker Department of Epidemiology and Biostatistics, University of Maryland School of Medicine, Baltimore, MD, USA
disease activity and QOL scores were similar between races. Conclusion We found that Caucasian and AA patients with CD had similar disease activity and QOL scores at initial presentation and over time. Thus, AA do not represent a more severe subgroup of CD patients to treat. These findings have important implications for clinicians that care for patients with CD. Keywords Healthcare disparities Inflammatory bowel disease Minority health Crohn’s disease
Introduction Inflammatory bowel disease (IBD) is a chronic inflammatory condition that targets the gastrointestinal tract, with higher incidence and prevalence rates reported in Caucasians compared to African Americans (AA). Ulcerative colitis (UC) and Crohn’s disease (CD), the two main subtypes, are estimated to affect over 1 million patients in the USA [1]. Despite the high prevalence in the USA, data regarding racial differences in disease phenotype, severity, surgical rates, extra intestinal manifestations, and medication use are scarce. Our current understanding of IBD epidemiology is based upon studies conducted in primarily Caucasian populations in North America and Europe, such as Olmsted County, MN, Manitoba, Canada, and Scandinavia [1]; studies evaluating IBD natural history, medication response, and surgical outcomes have also been conducted in [90 % Caucasian populations [2–5]. Since 2005, there has been a rise in published studies to elucidate racial differences between Caucasians and AA. Among studies, 11.2–37 % of patients were AA [6–12].
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Previous studies on differences in disease severity have not used validated clinical indices of disease activity. Surrogate markers of disease severity such as use of steroids, hospitalization, and surgery have revealed conflicting results. Two studies found no differences in disease severity by race [7, 12]; however, differences in health care utilization practices and impact on quality of life (QOL) have been observed [12]. A review of hospital discharges of IBD patients residing in San Francisco, CA, revealed an overall trend toward increasing hospitalizations in minorities from 1994 to 2006, including AA [11]. Though AA appear to have overall lower rates of bowel resection compared to Caucasians, the latter have experienced a 50 % decline in bowel resections from 1998 to 2003, a trend that was not observed in AA [13]. Deveaux et al. [14] also reported similar mean operations and frequency of surgery by race. CD behavior may also serve as a surrogate marker of disease severity. A review of IBD database from University of Chicago in 1971 demonstrated a threefold increase in the risk of perianal complications in AA patients compared to Caucasians [15]. Higher rates of fistulizing CD have been found in adult AA patients from the Jewish Hospital in St Louis, MO, and in pediatric AA patients from Georgia [16, 17]. Larger series have reported rates of perianal disease in AA patients that are equal to those of Caucasians [14, 18]. There are no data from prospective cohorts and clinical trials about differences in disease activity and QOL using validated indices of disease activity. The objective of this study was to assess for racial differences in disease activity and QOL over time among CD patients in a tertiary referral practice.
Materials and Methods Design We performed a retrospective cohort study of adult outpatients with CD evaluated at the University of Maryland, Baltimore IBD Program between July 1, 2004 and December 31, 2009. Identification of Subjects Confirmation of the diagnosis of CD was made following review of the patient’s medical records using standard clinical, radiologic, pathologic, and endoscopic criteria [19]. Patients who had indeterminate colitis or ulcerative colitis were excluded. Race was determined by patient report as Caucasian (non-Hispanic) or African American. Patients at the University of Maryland, Baltimore, respond to a single question regarding race on a Patient Health
123
Questionnaire. This response is scanned into an IRBapproved clinical data repository. The clinical data repository is a prospectively collected data repository that includes information on demographics, disease duration, IBD phenotype, extraintestinal manifestations of disease, medication exposure, hospitalizations, and surgeries. CD disease activity is assessed at each visit using the Harvey Bradshaw Index (HBI). Disease-specific QOL is measured at each visit using the Short Form Inflammatory Bowel Disease Questionnaire (SIBDQ) [20]. We identified Caucasian and AA CD patients who had greater than or equal to two valid scores for the HBI (C0) and SIBDQ (10–70) at two consecutive clinic visits. Data Analysis Baseline differences in participant characteristics by race were assessed using t tests for continuous variables and chi-square or Fisher’s exact test as appropriate for categorical variables. Clinic visits occurred as needed for proper clinical care, not on a set study schedule, and were therefore grouped into visit windows in order to make comparisons. The first visit during the study time frame was considered the baseline visit (Day 0). Visit windows were calculated based on number of days since the first visit that occurred in the study time frame (Day 0, Day 1–90, 91–180, 181–270, 271–360, 361–540, 541–720, 721–900, Day 901–1080). If multiple clinic visits occurred during a visit window, the disease activity and QOL values were used for the last visit in the window. If a patient was missing values for a given visit window, and had values for a subsequent visit window, the values from the most recent visit window were carried forward. Values were not carried forward if a patient did not have any subsequent visits. Preliminary graphs indicated that the relationship between disease activity/QOL and time changed between the first 180 days and the remainder of the study period. A spline was added after the Day 90–180 visit window to allow for this modification of the relationship. Two analyses were conducted separately. First, the relationship between disease activity and race over time was examined. Secondly, the relationship between QOL and race over time was examined. In each case, the relationship was assessed using a generalized estimating equation regression with robust variance estimation to correct for correlations caused by multiple clinic visits for each patient. Regressions included race, time, a spline at 180 days, the interaction between race and time, and the outcome variable of interest. All statistical tests were two sided. p values \0.05 were considered statistically significant. All statistical analyses were conducted with Stata 10 software (Stata Corporation, College Station, TX).
Dig Dis Sci Table 1 Baseline characteristics of patients with Crohn’s disease evaluated at the University of Maryland, Baltimore IBD Program between July 1, 2004 and December 31, 2009 (n = 296)
Characteristic
Total (n = 296)
White (n = 240)
African American (n = 56)
Male
116
99 (41)
17 (30)
Female
p value*
n (%) or mean ± SD Gender
0.13 180
141 (59)
39 (70)
Age at diagnosis (years)
28 ± 14
29 ± 14
26 ± 14
0.15
Current age (years)
40 ± 14
41 ± 14
40 ± 15
0.67
Never
163 (55)
128 (53)
35 (63)
Former
65 (22)
54 (23)
11 (20)
Current
68 (23)
58 (24)
10 (18)
99
84 (38)
15 (31)
Smoking status
0.44
Phenotype Location L1, ileal
0.46
L2, colonic
49
44 (20)
5 (12)
L3, ileocolonic
114
91 (42)
23 (55)
43
36 (15)
7 (15)
Location modifier L4, isolated upper disease
0.83
Behavior
0.08
B1, non-stricturing
89
79 (33)
10 (18)
B2, stricturing
108
85 (36)
23 (42)
B3, Penetrating
95
73 (31)
22 (40)
80
60 (25)
20 (36)
Behavior modifier P, Perianal disease
0.13
Presence of any EIM (except gallstones, arthralgias)
0.46
Yes
86
72 (30)
14 (25)
No
210
168 (70)
42 (75)
Prednisone
249
194 (80)
55 (20)
0.96
Immunomodulatorsa
218
173 (79)
45 (21)
0.33
Biologics
196
152 (78)
44 (22)
0.81
Infliximab
178
135 (76)
43 (24)
0.28
Adalimumab
81
64 (79)
17 (21)
0.79
Certolizumab pegol
9
5 (56)
4 (44)
0.09
Natalizumab
1
1 (100)
0 (0)
0.59
Medication exposure
a
Immunomodulators include 6-mercaptopurine (mp), azathioprine, and/or methotrexate (MTX) * p values from chi-square test, Fisher’s exact test, or t test, as appropriate
Results Participant Demographics Two hundred ninety-six patients with CD were identified who met the inclusion criteria. AA comprised 19 % (56/ 296) of the cohort. Detailed characteristics of all CD patients are listed in Table 1. There was no difference by race in gender, age at diagnosis, current age, smoking status, disease location, or the presence of extraintestinal manifestations of disease (excluding gallstones and arthralgias). There were no differences in medication exposure between races. A higher proportion of AA had penetrating
and stricturing disease behavior and perianal involvement compared to Caucasians; however, the differences were not statistically significant (Table 1). Differences in Disease Activity Between Caucasians and AA At baseline, Caucasians had a mean HBI score of 6.3 ± 5.2 (compared to 7.0 ± 5.6 for AA) (p = 0.43). In the first 180 days, the HBI score of Caucasians decreased 2.1 points and that of AA decreased 1.6 points (p \ 0.01 and p = 0.01, respectively, compared to baseline) (p = 0.44). The difference in the average decrease in HBI score in the
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Fig. 1 HBI scores over time in Caucasians and AA with Crohn’s disease
Fig. 2 SIBDQ scores over time in Caucasians and AA with Crohn’s disease
first 180 days is not statistically significant by race. After the first 180 days, the HBI score of Caucasians decrease 0.3 points with each increase of 180 days (p \ 0.01), and the change from the first 180 days is statistically significant (p \ 0.01). Similarly, the HBI score of AA decreases 0.2 with each visit window (p = 0.54). The relationship between the HBI score in the first 180 days and remaining time in the study is not different by race (p = 0.64). The data are descriptively depicted in Fig. 1.
time by race in individuals with CD. Within 6 months of initiating care at a tertiary referral center, we found that both AA and Caucasians had significantly reduced disease activity and improved QOL. In subsequent time periods, these trends persisted in both AA and Caucasians; however, the results were significant only in Caucasian patients. No differences in disease activity or QOL scores were noted by race at any time point post-baseline. To our knowledge, this study is the first to evaluate for racial differences in disease activity and QOL over time using validated disease activity and QOL indices. Previous literature has published conflicting results regarding differences in disease severity by race using surrogate measures of activity/severity such as disease behavior, steroid use, hospitalizations, and surgery. In contrast to our study, prior studies have reported differences in disease behavior by race. In a large North American cohort, a higher rate of perforating disease behavior was found in Caucasians compared to AA (30 vs. 19 %). Nguyen et al. [10] found that AA had a higher rate of obstructing disease behavior compared to Caucasians (38 vs. 24 %). Conversely, others have not detected differences in disease behavior. In a cohort of patients presenting for surgical procedures, Deveaux et al. [14] found similar rates of fistulizing complications. Kugathasan et al. [21] found similar phenotypic features of CD among AA and Hispanic children compared with white children. Moreover, prior studies have reported a greater prevalence of perianal involvement in AA [10, 12, 15]. Although the rate of perianal involvement was greater in AA in our study, the difference was not significant to reflect meaningful comparisons. The use of differing criterion to describe perianal CD may explain the differences among studies, as other studies have utilized a broader definition of perianal involvement. Previous literature has published conflicting results regarding differences in disease severity by race using
Difference in Disease-Specific Quality of Life Between Caucasians and AA At baseline, Caucasians had a mean SIBDQ score of 43.2 ± 14, compared to 40.8 ± 15 for AA (p = 0.32). In the first 180 days, the SIBDQ scores of Caucasians increase by 6.1 points (p \ 0.01 compared to baseline). Similarly, the SIBDQ score of AA increases by 6.6 points in the first 180 days (p \ 0.01 compared to baseline). The difference in the average increase in SIBDQ score in the first 180 days was not different by race (p = 0.80). After the first 180 days, the SIBDQ score of Caucasians increases, on average, 1.4 points with each increase of 180 days (p \ 0.01). Similarly, the SIBDQ score of AA increases, on average, 1.2 points with each increase of 180 days (p \ 0.01). The change in the average amount of SIBDQ increase between the first 180 days and the remaining time in the study is statistically significant (p \ 0.01) for both Caucasians and AA. This relationship was not statistically significantly different by race (p = 0.76). The data are descriptively depicted in Fig. 2.
Discussion This retrospective study of prospectively collected data showed no differences in the disease activity or QOL over
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other measures of disease activity such extraintestinal manifestations, hospitalizations, and surgery. A large multicenter analysis found a lower rate of surgery among AA compared to Caucasians; this racial difference persisted after adjustment for disease behavior and location [10]. Others have identified similar [7, 12] or increased rates of surgery when comparing races [17]. Nguyen et al. [10] also found obvious differences in the distribution of EIM among IBD patients, such as a four-fold greater prevalence of uveitis, and higher rates of sacroiliitis in AA compared to Caucasians. We did not compare differences in surgical rates by race in this study. We did evaluate EIM by race but found no racial differences in the distribution of EIM. However, our study is limited by significantly smaller number of participants. A systematic review of previously published literature found that the prevalence of joint problems, the most common EIM in both populations, was similar by race [22]. A subsequent systematic review of six published studies identified few differences between Caucasians and AA, namely a higher rate of skin and joint manifestations in AA [23]. Differences in treatment have been proposed as a possible etiology for differing severity of disease. Some single center studies have found no overall differences in medical treatment between Caucasians and AA [6, 11], while others found trends toward lower odds of treatment with infliximab (IFX) and immunomodulators [6-mercaptopurine(6MP)/azathioprine (AZA)] [8]. Steroid use did not seem to differ between races in these studies suggesting comparable disease severity. Our study found no differences in medication exposure at a single time point by race. An evaluation of medication exposure at differing time points may have been helpful in determining whether there are parallel changes in medication exposure as QOL and disease activity improve. Our study has several important strengths. The University of Maryland, Baltimore IBD program, has a higher proportion of AA patients with IBD and CD compared to other centers. We used validated indices rather than surrogate markers of disease activity to assess disease activity over time. Though the study design is retrospective, we used prospectively collected data regarding disease activity and QOL. Our study had several limitations. First, despite the comparatively high proportion of AA patients with CD, we still had a small absolute number of patients for analysis. This may limit the ability to detect small to moderate differences in disease activity or QOL by race. Although our length of follow-up was reasonable, on average, we do not have more than 3 years of follow-up data to identify later changes in disease activity. Further, because our cohort study began at the time of initial visit to our program, we cannot evaluate differences in disease activity at various time points in the disease process (early vs. late
activity). Lastly, even though we used validated disease activity indices, symptom-based activity indices themselves have limitations. It is possible that higher disease activity scores do not actually represent disease activity but relate to superimposed irritable bowel syndrome, antecedent viral syndromes, or other causes of elevated activity scores. Although possible, it is unlikely that there are significant differences in symptom-based reporting of CD symptoms by race. In summary, we found that Caucasian and AA patients with CD had similar disease activity and QOL scores at presentation to a referral center. Likewise, disease activity and QOL improved in both racial groups over time. These findings have important implications for clinicians that care for patients with IBD. First, we cannot confirm differences in disease activity between Caucasians and AA with CD. Thus, AA do not represent a more or less severe subgroup of CD patients to treat. Second, it does not appear that racial differences in previously utilized surrogate markers of disease behavior, such as penetrating phenotype, perianal complications, or EIMs exist in our cohort of patients, thereby lending further support to the notion that AA are not a more severe subgroup of CD patients. Further research is needed to identify reasons for disparities in treatment such as patient or provider bias or access to care issues. Conflict of interest
None.
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