Opiate use for inflammatory bowel disease (IBD), particularly high-dose (HD) use, is associated with increased mortality. It's assumed that opiate use is directly related to IBD-related complaints, although this hasn't been well defined. Our goal was to determine the indications for opiate use as a first step in developing strategies to prevent or decrease opiate use.
A retrospective cohort was formed of adults who were diagnosed with IBD and for whom outpatient evaluations from 2009 to 2014 were documented. Opiate use was defined if opiates were prescribed for a minimum of 30 days over a 365-day period. Individual chart notes were then reviewed to determine the clinical indication(s) for low-dose (LD) and HD opiate use.
After a search of the electronic records of 1,109,277 patients, 3,226 patients with IBD were found. One hundred four patients were identified as opiate users, including 65 patients with Crohn's and 39 with ulcerative colitis; a total of 134 indications were available for these patients. IBD-related complaints accounted for 49.25% of the opiate indications, with abdominal pain (23.13%) being the most common. Overall, opiate use for IBD-related complaints (81.40% vs. 50.82%;
Our findings show that most IBD patients using opiates, particularly HD users, used opiates for IBD-related complaints. Future research will need to determine the degree to which these complaints are related to disease activity and to formulate non-opiate pain management strategies for patients with both active and inactive IBD.
Inflammatory bowel disease (IBD) is characterized by spontaneous or chronic intestinal inflammation. The two major types of IBD are UC, which is limited to the colon, and CD, which can affect any segment of the gastrointestinal tract. Common disease manifestations include abdominal pain, diarrhea, bleeding, and weight loss. Extraintestinal manifestations of IBD are also common and can involve nearly any organ system, but they most commonly affect the joints, skin, and eyes. Apart from primary bowel complaints, extraintestinal manifestations may lead to loss of function and pain, posing additional challenges to physicians treating these patients.
The primary approach to managing IBD-related complaints is treatment of the disease itself. Although the more widespread use of immune modulators and newer biologic therapies has improved response rates and prevented disease-related complications,
IBD pain management is unfortunately complicated by evidence that commonly used analgesic medications such as NSAIDs may aggravate the disease.
The recent Crohn's therapy, resource, evaluation, and assessment tool (TREAT) registry update, which prospectively followed 6,273 CD patients for a mean duration of 5.2 years, demonstrated an association between opiate use and an increased risk of death in the CD population (hazard ratio [HR], 1.79; 95% CI, 1.29–2.48;
More recently, a retrospective case/control analysis of the large Manitoba IBD database of 4,217 subjects (1,996 CD and 2,221 UC patients) over a median review period of 6.5 years also showed an increased risk of mortality associated specifically with high-dose (HD) opiate use, which was defined as a morphine equivalent dose of >50 mg/day (HR, 2.82; 95% CI, 1.58–5.02).
Although there is no information on the harmful effects of opiates in IBD patients, it is clear that opiate use is more prevalent among the IBD population than among the general community, and it is associated with an increased mortality rate. While it is likely that opiate use among IBD patients is largely driven by IBD-related complaints, there is limited information on the indications for opiate use in IBD patients. We aimed to characterize the indications for opiate use as a first step in formulating strategies to prevent or decrease opiate use among IBD patients.
We formed a retrospective cohort of outpatients who visited the Northwell Health System. The health system coverage area includes over 10 million people, mainly from the New York metropolitan area. Data from January 1, 2009 to November 10, 2014 was collected from Allscripts, the outpatient electronic medical records (EMR) system. All adult patients with IBD who were >18 years old were identified by an International Classification of Disease (ICD-9) diagnostic code prefix of 555 for CD or 556 for UC. Patients with IBD were then defined as opiate users if they had a documented or electronically ordered opiate prescription for at least 30 days during the study period. The patients identified as opiate users were then further sub-categorized as either LD or HD users. The opiate dose was converted to morphine equivalents by using standard conversion formulas (
After identifying the IBD patients, each visit record corresponding to an opiate prescription order or documentation of use was analyzed for indications for opiate use. First, indications for opiate use were defined by an ICD-9 code in the EMR that linked the prescription order to a diagnosis or complaint. Opiate use could be linked to more than one diagnosis or complaint. Second, the medical provider chart notes corresponding to an opiate prescription order or documentation of use were reviewed to determine additional indications for opiate use. Patients were excluded if no clinical visit notes written by medical providers were available in the EMR system. If a patient had records of multiple clinical visits with documented opiate prescriptions, only the dose and indication(s) recorded in the clinical notes for the first visit were used for the main analysis. Additionally, usage of other IBD medications within 60 days of the opiate prescription was documented and analyzed. The medication categories were as follows: aminosalicylates, corticosteroids, immunomodulators, or biologics. Aminosalicylates included sulfasalazine and mesalamine (5-aminosalicylic acid) compounds taken orally, as enemas, or as suppositories. Immunomodulators included azathioprine, 6-mercaptopurine cyclosporine, tacrolimus, and methotrexate. Biologics included adalimumab, certolizumab, golimumab, infliximab, and vedolizumab. The study was approved by the Northwell Hofstra School of Medicine Institutional Review Board.
Structured chart reviews were performed for patients with IBD and documented opiate use. Observational analysis was used to compare data between the LD and HD opiate users. IBD- and non-IBD-related issues were grouped by opiate use categories. The cumulative number of complaints/diagnoses cited exceeded the number of patients; therefore, two separate analyses, one of the clinical complaints and another of the patients, were conducted. Statistical significance was determine by using Fisher exact test, and continuous variables were expressed as means±SD.
The cohort of active patients in Allscripts from January 1, 2009 to November 1, 2014 included 1,109,277 subjects, of which 3,226 were diagnosed with IBD. A total of 111 patients were identified as opiate users. Of these, seven were excluded from the analysis because the opiate dose was not documented. Thus, 65 (62.5%) patients with CD and 39 (37.5%) with UC were included in the analysis. A majority of the opiate users were women (54.8%,
The 104 patients reported a total of 134 complaints linked to opiate use. An analysis by complaints of the entire IBD group, as well as the LD and HD user subgroups, revealed abdominal pain to be the most commonly cited complaint linked to opiate use, accounting for 23.13% of the reported indications for opiate use (
Abdominal pain (44.19% vs. 19.67%,
The analysis of our population-based cohort revealed the clinical indications for opiate use in patients with IBD. Opiate use for IBD has been associated with poor clinical outcomes. Although it was assumed that opiate use in the IBD population is related to IBD activity and its complications, our study is the first to directly establish this link. IBD-related complaints accounted for roughly half of the cited clinical indications for prescribing opiates in our IBD cohort as well as in the LD and HD opiate use subgroups. When analysis was conducted on a per-patient basis instead, it was found that almost two-thirds of the patients cited an IBD-related complaint as a reason for their opiate use, with this figure rising to 81% among the HD patients. The significantly higher use of IBD medications among HD users indirectly indicates that IBD activity or complaints could be the main factor influencing opiate use. Expectedly, abdominal pain was the most common indication for opiate use, particularly among CD patients, and was cited by almost half of the HD users. Perianal complaints were also commonly attributed to opiate use in the CD group. Notably, in contrast to traditional assumptions, diarrhea was rarely documented as an indication for opiate use by the prescribing physician or as relayed to the physician.
Other studies have examined the clinical features of IBD and opiate use, reporting important associations between IBD and co-morbid disease; however, they did not precisely define the indications for opiate use. Early work presented by Kaplan and Korelitz
The main advantage of our study design was the use of population-based data available through the EMR system. After analyzing over 1.1 million subjects, we were able to identify 3,226 patients who had a diagnosis of IBD. While the IBD diagnosis was not validated by an additional review of the medical records, the observed prevalence of IBD of approximately 0.3% in our population was similar to the rate in the US population as a whole.
Although opiate use in IBD has previously been associated with comorbidities such as smoking, substance abuse, and psychiatric diseases, the indications for use have been poorly defined. Our analysis of a non-referral center, population-based IBD cohort shows that IBD complaints, especially abdominal pain, are the most common indications for opiate use, particularly among HD users. While it is unknown if HD opiate use causes direct harm to patients, it should be assumed. Opiate use, irrespective of the reason, should be treated as a red flag, and physicians should thoroughly reevaluate cases to determine evidence of active disease and modify treatment accordingly. In cases where evidence of active disease is absent, early consultation with pain management specialists is recommended to help the patient limit or eliminate opiate use. Future research should address non-opiate pain management strategies for IBD-related pain along with an emphasis on early, highly effective IBD therapy to prevent the disease complications that would lead to opiate use.
Oral Opioid Analgesic Equivalence Tablea
Variable | Total opiate use | Low-dose opiate use | High-dose opiate use | |
---|---|---|---|---|
No. of patients | 104 (100.00) | 61 (58.65) | 43 (41.34) | |
Sex | 0.5306 | |||
Male | 47 (45.19) | 26 (42.62) | 21 (48.84) | |
Female | 57 (54.81) | 35 (57.38) | 22 (51.16) | |
Age (yr) | 0.0638 | |||
<60 | 65 (62.50) | 43 (70.49) | 22 (51.16) | |
≥60 | 39 (37.50) | 18 (29.51) | 21 (48.84) | |
CD | 65 (62.5) | 40 (65.57) | 25 (58.14) | 0.9590 |
UC | 39 (37.5) | 21 (34.43) | 18 (41.86) | - |
Values are presented as number (%).
a
Medication | Total opiate use | Low-dose opiate use | High-dose opiate use | |
---|---|---|---|---|
Aminosalicylatesb | 22 (21.15) | 16 (26.23) | 6 (13.95) | 0.1312 |
Corticosteroids | 15 (14.42) | 4 (6.56) | 11 (25.58) | 0.0065 |
Immunomodulatorsc | 12 (11.54) | 3 (4.92) | 9 (20.93) | 0.0254 |
Biologicsd | 39 (37.50) | 15 (24.59) | 24 (55.81) | 0.0012 |
More than one medication | 14 (13.46) | 3 (4.92) | 11 (25.58) | 0.0024 |
Using any IBD medication | 74 (71.15) | 35 (57.38) | 39 (90.70) | 0.0030 |
Values are presented as number (%).
a
bIncludes sulfasalazine and 5-aminosalicylic acid compounds taken orally, as enemas, or as suppositories.
cIncludes azathioprine, cyclosporine, tacrolimus, and methotrexate.
dIncludes adalimumab, certolizumab, golimumab, and infliximab.
Variable | CD | UC | |
---|---|---|---|
No. of patients | 65 | 39 | - |
Sex | 0.1696 | ||
Male | 26 (40.00) | 21 (53.85) | |
Female | 39 (60.00) | 18 (46.15) | |
Age (yr) | 0.8360 | ||
≤30 | 8 (12.31) | 7 (17.95) | |
31–45 | 13 (20.00) | 6 (15.38) | |
46–60 | 21 (32.31) | 10 (25.64) | |
61–75 | 15 (23.07) | 11 (28.21) | |
≥76 | 8 (12.31) | 5 (12.82) |
Values are presented as number (%).
Complaint | Total | Low-dose opiate use | High-dose opiate use | |
---|---|---|---|---|
Total | 134b | 71 (53) | 63 (47) | - |
Abdominal pain | 31 (23.13) | 12 (16.90) | 19 (30.16) | 0.0693 |
Perianal fistula/abscess | 13 (9.70) | 8 (11.27) | 5 (7.94) | 0.5155 |
Pain due to post-IBD surgery | 9 (6.72) | 1 (1.41) | 8 (12.70) | 0.0128 |
IBD-related arthritis | 7 (5.22) | 6 (8.45) | 1 (1.59) | 0.1198 |
Erythema nodosum, iritis, pyoderma gangrenosum | 4 (2.99) | 3 (4.23) | 1 (1.59) | 0.6220 |
Diarrhea | 2 (1.49) | 1 (1.41) | 1 (1.41) | 1.0000 |
Total IBD indications | 66 (49.25) | 31 (43.66) | 35 (55.56) | 0.1693 |
Pain due to post non-IBD surgery | 4 (2.98) | 3 (4.23) | 1 (1.59) | 0.6220 |
Osteoarthritis | 18 (13.43) | 11 (15.49) | 7 (11.11) | 0.4578 |
Kidney stones | 7 (5.22) | 6 (8.45) | 1 (1.59) | 0.1198 |
Back pain | 10 (7.46) | 6 (8.45) | 4 (6.35) | 0.7490 |
Otherc | 29 (21.64) | 14 (19.72) | 15 (23.81) | 0.5660 |
Total non-IBD indications | 68 (50.75) | 40 (56.34) | 28 (44.44) | 0.1693 |
Values are presented as number (%).
a
Indications for opiate use | Total opiate use (n=104) | Low-dose opiate use (n=61) | High-dose opiate use (n=43) | |
---|---|---|---|---|
Patients with abdominal pain | 31 (29.81) | 12 (19.67) | 19 (44.19) | 0.0071 |
Total patients with an IBD indication | 66 (63.46) | 31 (50.82) | 35 (81.40) | 0.0014 |
Values are presented as number (%).
a
Indication for opiate use | Total patients (n=104) | CD (n=65) | UC (n=39) | |
---|---|---|---|---|
Patients with abdominal pain | 31 (29.81) | 25 (38.46) | 6 (15.38) | 0.0127 |
Total patients with any IBD indication | 66 (63.46) | 47 (72.31) | 19 (48.72) | 0.0156 |
Values are presented as number (%).
a