1. Opiate Usage Trends in Rheumatoid Arthritis (RA) compared to non-
RA: a Population Based Study 2004-2014
Table 3
Figure 1
• These findings suggest that subsequent years may show an epidemic
proportion of opiate use among patients with RA, which is higher than
in the general population, and with it the harm inherent with chronic
opiate therapy to include significant morbidity/mortality from
unintentional overdose.
• These findings may indicate that there are alternative pain pathways
closely related to the chronic inflammatory disease of RA, which are
not addressed with current therapies or properly predicted by
traditional disease severity measures.
• Alternative pain management therapies must be researched and
developed for patients with RA as they are at a high risk of relying on
opiates for long-term pain management; which itself has not been
properly studied in this population and truth about its therapeutic value
is ambiguous at best.
Discussion
• Over a third of patients with RA will use some form of opiate therapy;
one out of every ten with RA will be on some form of chronic opiate
therapy and moreover this number is steadily increasing.
• Of greatest concern is the increased opiate use among young adults
with RA (18-49 years old) and according to the CDC the persons at
highest risk to suffer harm from opiate use are all those aged 65 years
or under who are prescribed therapy for 6 weeks (or longer) and all
those using extended-use formulations of opiates such as fentanyl
patches, extended release oxycodone, and methadone (3).
• RA disease severity indicators and therapies (except for
glucocorticoids) were not associated with opiate use, suggesting that
other factors significantly impact the need for and use of opiates for
pain management in RA.
Conclusions
1. Nelson, L. S. and J. Perrone (2012). "Curbing the opioid epidemic in the United States:
the risk evaluation and mitigation strategy (REMS)." JAMA 308(5): 457-458.
2. CDC.(2015). "NCHS Data on Drug Poisoning Deaths." from
http://www.cdc.gov/nchs/data/factsheets/factsheet_drug_poisoning.pdf.
3. Jones, C. M., K. A. Mack, et al. (2013). "Pharmaceutical overdose deaths, United States,
2010." JAMA 309(7): 657-659
References
Background: Recent years have seen a dramatic increase in
opiate prescriptions across the United States with sales
quadrupling in the years between 1999 and 2010 (1). Along with
this explosive growth in prescription sales of opiates, opiate drug
poisoning death rates, 81% of which were unintentional, have
more than doubled from 2000 to 2013, from 6.2 to 13.8 per
100,000 (2).
Patients with rheumatoid arthritis (RA) suffer from chronic pain.
However, it is not clear to what extent they use opiates to help
manage their pain. We undertook this study to describe risk factors,
patterns and time trends for opiate use in this patient population,
and compare them to opiate use in the general population.
Objectives: 1) To identify trends of opiate use over time in a
modern well-established and well–defined population of patients
with RA, and compare them to age and sex comparator subjects.
2) To identify patients with RA who are at greatest risk of chronic
opiate use and to describe associations of opiate usage trends
with: disease severity (i.e. erosive joint damage), socioeconomic
status, smoking, and medically treated depression and
fibromyalgia.
Study Population: RA and non-RA subjects were gathered from
the Rochester Epidemiology Project (REP), a records-linkage
system that records all inpatient and outpatient encounters among
the residents of Olmsted County, Minnesota. All RA subjects met
the 1987 American College of Rheumatology criteria.
Data Collection: Utilizing electronic REP resources, all outpatient
opiate prescriptions were identified (generic and trade names) for
2004 - 2014.
Definitions: Any opiate use was defined as one or more opiate
prescriptions in the study period. Chronic use was defined as ≥60
days of prescribed opiates at usual dose and usual schedule
(Table 1) in a 6 month period or subjects using fentanyl,
methadone and controlled/sustained release oxycodone. After
having met our definition of chronic use, subjects were returned to
non-chronic use when there was a year without an opiate
prescription. The index date for all subjects was 1/1/2005.
Patients who had any opiate prescription in 2004 were excluded
from analyses of chronic use.
Statistical Methods: Person-year methods and Cox models
adjusted for age, sex and other characteristics were used to
examine differences in opiate use between the cohorts. Cox
models were also used to examine predictors of chronic opiate use
among the patients with RA.
Methods & Objectives
• A total of 501 patients with RA (71% female) and 532 non-RA
subjects (70% female) were included in the study. The RA patients
had a mean age at index date of 61.3 ± 14.5 years, with a mean
follow-up from index of 8.5 ± 2.4 years. The non-RA subjects had a
mean age at index date of 62.6 ± 14.7 years, with a mean follow-up
from index of 8.7 ± 2.4 years. The 156 patients with RA and 105
non-RA subjects who had an opiate prescription in 2004 were
excluded from analyses of chronic opiate use.
• The opiates identified in our study, by prescription frequency, were
oxycodone (39%), hydrocodone (18%), tramadol (22%), fentanyl
(6%) morphine (3%), propoxyphene (4%) and codeine (5%).
• Total opiate use (any) was found to be high in both cohorts. 40% of
patients with RA and 24% non-RA subjects had used opiates in 2014.
Patients with RA had a markedly (58%) higher rate of any opiate use
when compared to non-RA subjects (Age and sex adjusted hazard
ratio [HR]: 1.58; 95% confidence interval [CI]: 1.37, 1.82; Figure 1a).
• Chronic opiate use was substantial in both cohorts, 12% RA vs 4%
non-RA in 2014. The number of patients with RA using chronic opiate
therapy was 90% higher than that of comparator subjects (Age and
sex adjusted HR 1.90; 95% CI: 1.32, 2.72; Figure 1b). After further
adjustment for smoking status, education, treatment for depression or
fibromyalgia, and Charlson comorbidity index, chronic opiate use
remained higher among patients with RA compared to non-RA
subjects (HR 1.92; 95% CI: 1.33, 2.78).
• Chronic opiate use was higher among both women and men with RA
compared to non-RA (Rate ratio [RR]: 1.80 and 1.46, respectively),
but this increase was not statistically significant among men (Table
2a).
• Chronic opiate use was significantly higher in younger patients with
RA (age 18-49 years) of 2.0% vs. 0.7% in non-RA young adults (RR:
2.76; 95% CI: 1.35, 6.39; Table 2b) with no identified difference in risk
of chronic opiate use between patients with RA and comparator
subjects for those over 65 years but a twofold increased risk in those
aged 50 to 64 years with RA (RR 2.03; 95% CI: 1.08, 4.03; Table 2b).
• The risk for chronic opiate use is highest among young adult females
with RA when compared to non-RA subjects (RR 3.59; 95% CI: 1.50,
11.08; Table 2c).
• There were no significant associations between smoking status,
education, treatment for depression or fibromyalgia, or RA disease
characteristics and chronic opiate use among patients with RA (Table
3). There was no association between biologic use and chronic opiate
use among patients with RA. Patients with RA using glucocorticoids
were more likely to be chronic opiate users.
Results
Table 2a
Table 2
Table 1
© 2015 Mayo Foundation for Medical Education and Research
J.A. Zamora-Legoff MD, Sara J. Achenbach MS, Cynthia S. Crowson MS, Megan L. Krause MD, John M. Davis III MD MS, Eric L. Matteson MD MPH
Division of Rheumatology
Mayo Clinic, Rochester, MN
Table 2a: First Chronic Opiate Use by Sex
Sex RA Rate Non-RA Rate RR (95% CI)
M 1.92 1.31 1.46 (0.73, 2.95)
F 2.56 1.42 1.80 (1.19, 2.75)
Total 2.37 1.39 1.71 (1.20, 2.45)
Table 2b: First Chronic Opiate Use by Age Group
Age Group RA Rate Non-RA Rate RR (95% CI)
18-49 2.02 0.71 2.76 (1.35, 6.39)
50-64 1.98 0.96 2.03 (1.08, 4.03)
65+ 3.60 2.81 1.28 (0.75, 2.18)
Total 2.37 1.39 1.71 (1.20, 2.45)
Table 2c: First Chronic Opiate Use by Age Group in Women
Age Group RA Rate Non-RA Rate RR (95% CI)
18-49 2.09 0.54 3.59 (1.50, 11.08)
50-64 1.97 0.93 2.06 (0.95, 4.89)
65+ 4.39 3.19 1.38 (0.76, 2.48)
Total 2.56 1.42 1.80 (1.19, 2.75)
Prediction of first chronic opiate use among patients with RA. Models are adjusted for age, sex,
and RA duration
Risk Factor HR (95% CI) P-value
Smoking Status (Reference = Never) 0.192
Former 1.23 (0.70, 2.15)
Current 1.75 (0.96, 3.22)
Highest Education (Reference = High School) 0.242
Graduate School 0.77 (0.80, 3.94)
Technical School/College 0.81 (0.47, 1.40)
< High School 1.33 (0.54, 3.27)
Treatment for Depression at Index 0.78 (0.34, 1.83) 0.575
Treatment for Fibromyalgia at Index 1.84 (0.58, 5.88) 0.301
Any Biologic Use Prior to Index 1.18 (0.55, 2.50) 0.670
Glucocorticoid Use at Index 2.48 (1.51, 4.06) <0.001
Usual dose and usual schedule definitions for opiate use