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The effects of physician specialty and patient comorbidities on the use and discontinuation of coxibs.

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Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 49, No. 3, June 15, 2003, pp 293–299
DOI 10.1002/art.11117
© 2003, American College of Rheumatology
The Effects of Physician Specialty and
Patient Comorbidities on the Use and
Discontinuation of Coxibs
Objective. To examine the effects of physician specialty and comorbidities on cyclooxygenase 2–selective nonsteroidal
antiinflammatory drugs (NSAIDs; coxibs) utilization.
Methods. Medical records of 452 patients from a regional managed care organization with >3 consecutive NSAID
prescriptions from June 1998 to April 2001 were abstracted. Multivariable adjusted associations between coxib initiation
and discontinuation and patient and provider characteristics were examined.
Results. A total of 1,142 NSAID prescriptions were written over 9,398 total patient-months of followup. Compared with
patients seeing family or general practitioners, patients seeing rheumatologists (odds ratio [OR] 3.4, 95% confidence
interval [95% CI] 2.1–5.7) and internists (OR 2.3, 95% CI 1.5–3.6) were significantly more likely to receive a coxib, as well
as patients with a history of osteoarthritis (OR 2.6, 95% CI 1.7–3.8), gastrointestinal disease (OR 2.3, 95% CI 1.2– 4.5), and
congestive heart failure (OR 4.1, 95% CI 1.0 –16.4). Although specialists were more likely than generalists to prescribe
coxibs, only family or general practitioners were significantly more likely to selectively use coxibs among their patients
with a history of gastrointestinal disease. Fifty-four percent of NSAID prescriptions were discontinued, and coxibs were
significantly less likely to be discontinued than were traditional NSAIDs (OR 0.6, 95% CI 0.5– 0.8).
Conclusion. Our findings suggest significantly greater, but perhaps less selective use of coxibs among specialists, even
after accounting for important covariates. The initiation and discontinuation of coxibs was influenced by physician
specialty and by patient risk factors.
KEY WORDS. Nonsteroidal antiinflammatory drugs; Coxibs; Practice pattern variation.
Nonsteroidal antiinflammatory drugs (NSAIDs) are among
the most frequently prescribed medication class worldwide (1– 8). Despite their popularity, patient safety remains a significant concern of chronic NSAID use (3,9 –
19). It is unknown, however, whether factors leading to
significant variation in safe physician practices observed
for other musculoskeletal therapies (5,20 –22) may also
influence use of the newer, potentially safer cyclooxygenase 2 (COX-2)–selective NSAIDs (or coxibs).
To identify associations with coxib use, we linked administrative, pharmacy, and medical record review data
for a sample of chronic NSAID users who were enrollees in
a regional managed health care organization. We hypothesized that risk factors for NSAID toxicity such as older age
Supported in part by grants from the NIH (P60-AR-2061423) and the Agency for Healthcare Research and Quality
Fausto G. Patino, MD, DrPH, Jason Olivieri, MPH, Amy
Mudano, MPH, Larry Moreland, MD: Center for Education
and Research on Therapeutics of Musculoskeletal Disorders, University of Alabama at Birmingham; 2Jeroan Allison, MD, MSc, Sharina Person, PhD, Kenneth G. Saag, MD,
MSc: Center for Education and Research on Therapeutics of
Musculoskeletal Disorders, Center for Outcomes and Effectiveness Research and Education, University of Alabama at
Birmingham; 3Lucia Juarez, MA, Stacey H. Kovac, PhD:
Center for Outcomes and Effectiveness Research and Education, University of Alabama at Birmingham; 4Ted R.
Mikuls, MD, MSPH: University of Nebraska, Omaha.
Dr. Saag has served as a paid consultant and has received
honoraria from Merck & Co.
Address correspondence to Kenneth G. Saag, MD, MSc,
Associate Professor and Director, Center for Education and
Research on Therapeutics of Musculoskeletal Disorders,
University of Alabama at Birmingham, Birmingham, AL
35294-3408. E-mail:
Submitted for publication March 30, 2002; accepted in
revised form August 14, 2002
and comorbidity would be positively associated with increased coxib prescriptions, and that rheumatologists
would be more likely than family or general practitioners
to prescribe coxibs. In addition, we explored the reasons
for discontinuation of NSAIDs.
Data sources and data collection. After approval by the
University of Alabama at Birmingham Institutional Review Board, we identified NSAID users from a sample of
participants from a large, regional managed health care
organization. National Drug Codes were used to identify
all NSAID prescriptions from pharmacy claims. Study patients were restricted to chronic NSAID users, defined as
persons receiving at least 3 consecutive nonaspirin NSAID
prescriptions over any time interval from June 1998 to
December 1999. To assess provider factors associated with
practice pattern variation, NSAID users were stratified
based on the specialty of their prescribing physician. We
focused on providers who were more likely to care for
chronic NSAID users (family or general practitioners, internists, and rheumatologists) and deliberately oversampled rheumatologists to address our hypotheses about
the role of provider factors. From a total of 2,334 eligible
patients using NSAIDs, 680 patients (29%) and their corresponding 136 providers (5 patients per provider) were
randomly selected.
Pharmacy claims data were initially used to identify
subjects. Sociodemographic factors, type of insurance coverage, as well as physician specialty and number of covered patients using NSAIDs, were collected from administrative claims and provider databases. Patients were
categorized into 2 groups according to the presence or
absence of a drug benefit associated with their insurance
plan. All subsequent analyses were based on data derived
from medical record review.
Medical record abstraction process. Medical record review included all chart documentation between June 1998
and April 2001. Trained nurse abstractors used a customized version of the MedQuest software (developed by Fu et
al under contract from the Health Care Financing Administration) for chart abstraction. Medical record abstractors
achieved 97% interrater reliability.
Medical history, physical examination signs, and comorbidities (when recorded in the chart), with special
attention to those that might predispose to NSAID use and
discontinuation, were collected. Particular attention was
devoted to NSAID use and medications that might adversely interact with NSAIDs or were markers for NSAID
renal toxicity (diuretics, angiotensin-converting enzyme
inhibitors) or were indicative of a predilection to NSAID
gastrointestinal (GI) toxicity (corticosteroids, cytoprotective drugs, H2 blockers, and proton pump antagonists).
NSAID use during the study period was defined as traditional (nonselective) NSAIDs only, or coxibs ever (including users of coxibs only and users of both types of medications). Intervals of use represented each uninterrupted
Patino et al
use of any NSAID during the followup period. One NSAID
could have more than one interval if the patient used the
drug intermittently. Cumulative use of NSAIDs represented the sum of NSAID interval periods, subtracting the
overlap periods (when a patient was taking more than one
NSAID). Information on NSAID use was restricted to prescription medication. Over-the-counter medications, such
as nonprescription NSAIDs and acetaminophen, were not
considered in this study.
Statistical analysis. Chi-square and one-way analysis of
variance or Student’s t-tests were used to describe categorical and continuous demographic, clinical, and NSAID
utilization variables, respectively. To determine predictors
of NSAID use and discontinuation, we performed multivariable logistic regression analysis using the model-building techniques described by Hosmer and Lemeshow (23).
Generalized estimating equations (24) were used to adjust
for artificial inflation of statistical significance resulting
from patients being nested within physicians. Due to their
clinical relevance, all multivariable analyses were adjusted for age and sex. For other variables, a bivariate P
value ⱕ0.25 was required to enter the models. Data management, reduction, and analyses were conducted in Microsoft Access (Microsoft Corporation, Redmond, WA),
SAS (SAS Institute, Cary, NC) and SPSS (SPSS, Chicago,
We received a total of 452 records (66% record response
rate) from 103 physicians (43 internists, 44 general and
family practitioners, 16 rheumatologists) (76% physician
response rate). There were no significant differences in sex
and age between patients whose records were reviewed
and those whose records were not provided.
A total of 1,142 NSAID prescriptions were written over
9,398 total patient-months of followup. Coxibs accounted
for 435 (38%) of all NSAID prescriptions. Characteristics
of the 452 NSAID users, stratified by type of NSAID used,
are shown in Table 1. Compared with traditional NSAID
users, coxib users were older, more likely to have history
of GI disease and osteoarthritis (OA), and trended toward
a higher prevalence of comorbidities and connective tissue
diseases. Use of other prescription analgesics showed no
association with use of coxibs. Patients using coxibs had a
significantly longer cumulative drug use as well as a longer
followup during the study period. Coxib ever users had
more intervals of use than did traditional NSAID only
users (2.9 versus 1.9; P ⬍ 0.001) (data not shown). There
was no significant difference in the use of coxibs based on
the type of drug benefit coverage; if anything, those with
limited or no drug benefit trended toward more frequent
coxib use.
Patients seen by internists were older than patients seen
by family or general practitioners and rheumatologists (see
Table 2). Those seen by rheumatologists were less likely to
have a history of diabetes or hypertension or to use antihypertensive medications.
Patients seen by an internist or rheumatologist were
Use and Discontinuation of Coxibs
Table 1. Characteristics of patients receiving traditional nonsteroidal antiinflammatory drugs versus coxibs*
Age, mean ⫾ SD, years
Number of concomitant drugs, mean ⫾ SD
Cumulative duration of NSAID use, mean ⫾ SD months
Number of observation months, mean ⫾ SD
Number of physician visits per 12 observation months, mean ⫾ SD
Sex, women
Conditions associated with NSAID toxicity
Congestive heart failure
Gastrointestinal disease
Renal diseases
Arthritis type
Rheumatoid arthritis
Lupus or connective tissue disease type unknown
Possible concomitant medications associated with NSAID toxicity
Angiotensin-converting enzyme inhibitors
Other antihypertensives
Other analgesics
Any of the above concomitant medications
Traditional NSAIDs
only users (n ⴝ 157)
Coxib ever users
(n ⴝ 295)
59.8 ⫾ 11.4
12.3 ⫾ 7.0
10.4 ⫾ 9.4
19.6 ⫾ 8.9
6.4 ⫾ 7.2
94 (59.9)
62.8 ⫾ 11.4†
14.5 ⫾ 8.9†
12.7 ⫾ 8.5†
21.4 ⫾ 7.4†
5.9 ⫾ 3.5
194 (65.8)
2 (1.3)
28 (17.8)
12 (7.6)
89 (56.7)
4 (2.5)
11 (3.7)
50 (16.9)
46 (15.6)‡
145 (49.2)
11 (3.7)
86 (54.8)
14 (8.9)
41 (26.1)
216 (73.2)§
30 (10.2)
99 (33.6)
40 (25.5)
41 (26.1)
69 (43.9)
37 (23.6)
3 (1.9)
64 (40.8)
124 (79.0)
78 (26.4)
98 (33.2)
113 (38.3)
58 (19.7)
6 (2.0)
125 (42.4)
236 (80.0)
* Except where indicated otherwise, values are the number (%). Coxib ever users were patients who received at least one prescription for rofecoxib
or celecoxib. Gastrointestinal disease includes peptic ulcer, gastritis, or gastrointestinal bleeding. NSAID ⫽ nonsteroidal antiinflammatory drug.
† P ⬍ 0.01.
‡ P ⬍ 0.05.
§ P ⬍ 0.001.
more likely to initiate coxibs referent to those seen by a
family or general practitioner (P ⬍ 0.001). This pattern
persisted among patients with a history of GI disease (Figure 1A) or hypertension (Figure 1B). Among patients with
either a history of GI disease or potential NSAID gastrointestinal risk factors (age ⱖ65 years, concomitant use of oral
corticosteroids), those seen by an internist or rheumatologist were significantly more likely to receive coxibs than
Table 2. Characteristics of patients receiving traditional nonsteroidal antiinflammatory drugs and coxibs by prescribing
physician specialty*
Physician specialty
Age, mean ⫾ SD, years
Comorbid conditions
Gastrointestinal disease
Congestive heart failure
Any of above comorbid conditions
Possible concomitant medications
Angiotensin-converting enzyme inhibitors
Other antihypertensives
Any of above concomitant medications
Family or general
(n ⴝ 184 patients)
(n ⴝ 194 patients)
(n ⴝ 74 patients)
57.8 ⫾ 12.5
69.9 ⫾ 9.4
60.8 ⫾ 10.0†
33 (17.9)
24 (13.0)
101 (54.9)
5 (2.7)
11 (60.3)
43 (22.2)
25 (12.9)
122 (62.9)
8 (4.1)
137 (70.6)
2 (2.7)‡
9 (12.2)
11 (14.9)†
0 (0.0)
20 (27.0)†
51 (27.7)
20 (10.9)
57 (31.0)
68 (37.0)
110 (59.8)
56 (28.9)
52 (26.8)
67 (34.5)
93 (47.9)
145 (74.7)
11 (14.9)
23 (31.1)†
15 (20.3)
21 (28.4)‡
44 (59.5)‡
* Except where indicated otherwise, values are the number (%). Gastrointestinal disease includes peptic ulcer, gastritis, or gastrointestinal bleeding.
† P ⬍ 0.001, by one-way analysis of variance or chi-square trend test.
‡ P ⬍ 0.01, by one-way analysis of variance or chi-square trend test.
Patino et al
Figure 2. Proportion of patients discontinuing nonsteroidal antiinflammatory drugs (NSAIDs), stratified by prescribing physician
specialty. * ⫽ P ⫽ 0.05, comparisons between all physician specialties.
coxib use within each physician specialty, family and
general practitioners but not internists or rheumatologists
were more likely to selectively prescribe coxibs rather than
traditional NSAIDs to their patients with a history of GI
disease (odds ratio [OR] 2.6, 95% confidence interval [95%
CI] 1.0 – 6.5) (Figure 1A). Only rheumatologists, however,
trended toward a preference for coxib selection over traditional NSAIDs for their patients with hypertension (Figure 1B).
In Table 3, after multivariable adjustment for potential
confounders, a history of OA, GI disease, or congestive
heart failure remained significantly and positively associated with initiation of coxibs. Even after adjustment for
these potential confounders, being seen by an internist or
rheumatologist was still a significant predictor of coxib
Figure 2 shows discontinuation of NSAIDs according to
prescribing physician specialty. Patients seen by family or
general practitioner were less likely to discontinue at least
one NSAID drug compared with patients seen by internists
Figure 1. Proportion of patients with gastrointestinal (GI) disease
(A) or hypertension (B) receiving coxibs, stratified by prescribing
physician specialty. GI disease includes peptic ulcer, gastritis, or
GI bleeding. † ⫽ P ⫽ 0.04, comparison within family or general
practitioners only. ‡ ⫽ P ⫽ 0.001, comparisons between all physician specialties.
were those seen by a generalist (P ⫽ 0.03 and P ⫽ 0.003,
respectively) (data not shown).
When comparing the use of nonselective NSAID versus
Table 3. Patient and provider characteristics associated with ever use of a coxib
Age, years
Sex (referent to men)
Rheumatoid arthritis, systemic lupus erythematosus,
or other connective tissue disease
Comorbid conditions
Gastrointestinal disease†
Congestive heart failure
Provider type
General or family practitioner
Insurance drug coverage
odds ratio
95% confidence
odds ratio*
95% confidence
* Includes age, sex, and variables with univariate P ⬍ 0.25 (osteoarthritis, comorbidities, provider type, insurance drug coverage).
† Gastrointestinal disease includes peptic ulcer, gastritis, or gastrointestinal bleeding. c statistic ⫽ 0.72 (47); Hosmer and Lemeshow goodness of fit
statistic P ⫽ 0.47 (48).
Use and Discontinuation of Coxibs
Table 4. Reasons for discontinuation of traditional nonsteroidal antiinflammatory drugs
and coxibs*
Traditional NSAIDs
(n ⴝ 707 prescriptions)
(n ⴝ 435 prescriptions)
411 (58.1)
204 (46.9)†
72 (10.2)
66 (9.3)
41 (9.4)
27 (6.2)
42 (5.9)
3 (0.4)
21 (3.0)
24 (3.4)
4 (0.6)
21 (3.0)
8 (1.8)†
5 (1.1)
14 (3.2)
3 (0.7)†
9 (2.1)§
6 (1.4)
Drug discontinued, n ⫽ 615
Known reason for discontinuation,
n ⫽ 273‡
Lack of efficacy
Adverse event
Type of adverse event
Other or not mentioned
Therapeutic course completed
Too expensive
Other factors
* Values are the number (%). Gastrointestinal events include abdominal pain, gastrointestinal bleeding,
or gastrointestinal complications. Non-gastrointestinal events include dyspnea, headache, dizziness,
renal complications, and central nervous system complaints. NSAIDs ⫽ nonsteroidal antiinflammatory
† P ⬍ 0.01.
‡ Explicit reason known for 44% of all NSAIDs discontinued.
§ P ⬍ 0.05.
(OR 0.5, 95% CI 0.2– 0.9) and rheumatologists (OR 0.6,
95% CI 0.4 – 0.9). However, patients of rheumatologists
were less likely to completely discontinue all of their
NSAIDs compared with patients seen by internists (OR
0.4, 95% CI 0.2– 0.9) or family and general practitioners
(OR 0.6, 95% CI 0.3–1.3).
Patients who stopped at least one NSAID medication
were more likely to have a history of GI disease (P ⫽ 0.004)
and a history of OA (P ⫽ 0.045). Stopping all NSAIDs was
not significantly associated with any of the patient characteristics examined (data not shown). Patients who had
documented complaints of GI problems or whose medical
record presented evidence of GI bleeding were more likely
to stop at least one NSAID prescription (n ⫽ 57; 83%) than
were patients for whom these complaints or medical findings were not documented (n ⫽ 260; 68%) (P ⫽ 0.014). A
similar trend was observed for discontinuation of all
NSAIDs (23% versus 18%) (data not shown).
We next examined patterns and predictors of NSAID
discontinuation at the individual prescription level (Table
4). Of all NSAID prescriptions written (n ⫽ 1,142), 615
(54%) were discontinued during followup after a mean ⫾
SD cumulative duration of 5.8 ⫾ 5.9 months per agent.
Compared with traditional NSAIDs (411 prescriptions;
58%), coxibs (204 prescriptions; 47%) were significantly
less likely to be discontinued (OR 0.6, 95% CI 0.5– 0.8). Of
the 615 documented NSAIDs that were stopped, 273 (44%)
had a documented reason for discontinuation. Among
these, lack of efficacy was the most frequent reason (n ⫽
113, 41%) followed by an adverse event (n ⫽ 93, 34%). GI
complaints (abdominal pain, GI bleeding, or GI complications) were the most frequently documented medical problems considered to be an adverse event by the managing
physicians (n ⫽ 50, 54%). There was no significant association between NSAID type (coxibs or traditional) and
reporting of an adverse event as a reason for discontinuation. Compared with coxibs, traditional NSAIDs were sig-
nificantly more likely to be discontinued because of a GI
adverse event (OR 4.2, 95% CI 1.6 –10.9) or a history of GI
disease (OR 1.7, 95% CI 1.1–2.6). In contrast, coxibs were
more likely to be discontinued when the patient had a
history of hypertension (OR 1.5, 95% CI 1.0 –2.1).
Multivariable regression analyses exploring reasons for
NSAID discontinuation showed that patients with a history of GI disease (OR 2.5, 95% CI 1.2–5.3) and those
seeing an internist (OR 1.7, 95% CI 1.0 –2.7) or a rheumatologist (OR 3.1, 95% CI 1.7–5.6) (referent to those seeing
a family or general practitioner) remained more likely to
discontinue at least one NSAID (data not shown).
Despite the increasing worldwide use of coxibs (25,26),
patterns and predictors of coxib use have not been previously studied at a population level. A plausible explanation for the greater use of coxibs by specialists in our study
is that internists (and particularly rheumatologists) see
referred patients who already have tried traditional
NSAIDs and either experienced no benefit or experienced
toxicity. It is also possible that these same patients are also
more likely to be exposed to and/or influenced by directto-consumer advertising. Practice pattern variations
among the therapies for musculoskeletal disorder are well
documented (20,22,27–29). Variations in practice patterns
and unequal levels of patient care may be partially attributable to inadequate dissemination of the latest knowledge. Specialists such as rheumatologists are quicker to
adopt new treatments when choosing medications
(22,27,30 –34).
It should be noted that of all pharmaceutical products
being marketed, rofecoxib had the largest recent advertising budget of any current pharmaceutical product (35).
Accordingly, rheumatologists and internists are more fre-
quently exposed to pharmaceutical detailing of newer arthritis products than are family or general practitioners,
and this may preferentially influence their prescribing behaviors.
Comorbidity, especially GI disease and cardiac failure,
appeared to be a factor favoring the selection of coxibs.
This may be a reflection of physicians prescribing these
medications to “sicker” patients. Our finding that generalists are more likely to selectively prescribe coxibs to their
patients at higher risk for GI disease is important, because
⬎60% of patients with musculoskeletal disorders are
treated primarily by generalists (36), and ⬎20% of all
encounters with primary care providers are for musculoskeletal complaints (37,38). Generalists tend to be more
conservative and often more cost-effective in their adoption of newer musculoskeletal therapies (30), which may
influence their willingness to selectively prescribe coxibs
to a patient with a history of GI disease.
Compared with nonselective NSAIDs, coxibs were significantly less likely to be discontinued, suggesting that
they may be better tolerated. During the first months of the
study period, only traditional NSAIDs were prescribed,
and it is possible that coxibs were too new to the drug
market and had not been used for a long enough time to be
as commonly discontinued. However, the duration of
NSAID use did not significantly differ between the 2
classes of drugs in our study.
GI problems have been consistently reported as the most
frequently documented adverse event leading to discontinuation of an NSAID (39). As expected, a history of GI
disease was the factor most associated with discontinuation of at least one NSAID. Although the numbers were
small, nonselective NSAIDs had more discontinuations for
GI reasons than did the coxibs. These findings support the
premise that GI symptoms or adverse effects may be a
major factor associated with switching between NSAIDs.
Absence of more comprehensive data on discontinuation
prohibits us from deeper exploration of these findings.
This study did not addresses important questions on
physicians’ prescribing behaviors, such as overprescription of NSAIDs or adherence to community standards of
care. We did not define absolute standards against which
to measure prescribing quality, because evidence on
which to generate consensus remains incomplete.
Because medical record review is constrained by the
completeness and accuracy of the information recorded
(40 – 42), our analysis may partially reflect quality of documentation rather than quality of care. In addition, medical charts do not provide accurate information on adherence to medical treatment or on the magnitude of use of
over-the-counter medications (43– 46). However, our detailed record review protocol with stringent quality control and excellent interrater reliability increase confidence
in our results. Another limitation in the present study is
that we were not able to ascertain patient race/ethnicity,
because the managed care organization did not routinely
collect racial or ethnic information. Last, given the restriction of our sample to one geographic area, our results may
not be generalizable to all groups of chronic NSAID users.
Despite these potential limitations, the data for this study
came from a large regional managed health care organiza-
Patino et al
tion, allowing linkage of data from medical records, pharmacy claims, and administrative files.
In conclusion, we observed significantly greater use of
coxibs among specialists, even after accounting for important case-mix covariates. We also determined that patient
factors, such as GI disease, had an important impact on
both initiation and discontinuation of traditional NSAIDs
compared with coxibs. Further research is needed to relate
these interesting NSAID use patterns with long-term patient safety.
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physicians, effect, patients, discontinuation, specialty, coxibs, comorbidities, use
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