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The effect of alcohol on radiographic progression in rheumatoid arthritis.

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ARTHRITIS & RHEUMATISM
Vol. 62, No. 5, May 2010, pp 1265–1272
DOI 10.1002/art.27388
© 2010, American College of Rheumatology
The Effect of Alcohol on Radiographic Progression in
Rheumatoid Arthritis
M. J. Nissen,1 C. Gabay,1 A. Scherer,2 and A. Finckh,1 for the Swiss Clinical Quality
Management Project in Rheumatoid Arthritis
0.99% (95% confidence interval [95% CI] 0.89–1.09) and
1.13% (95% CI 1.01–1.26) at 1 year, respectively. Alcohol
consumption displayed a J-shaped dose-response effect,
with a more favorable evolution in occasional consumers (P ⴝ 0.01) and daily consumers (P ⴝ 0.001) as
compared with nondrinkers, while heavy drinkers demonstrated worse radiographic evolution (P ⴝ 0.0001).
We found significant effect modification by sex, with
male drinkers displaying significantly less erosive progression compared with male nondrinkers (mean 0.86%
[95% CI 0.70–1.03] versus 1.35% [95% CI 1.02–1.67];
P ⴝ 0.007).
Conclusion. Our findings indicate a trend toward
reduced radiographic progression in alcohol drinkers
compared with nondrinkers, specifically in occasional
and daily alcohol consumers. In particular, male patients with RA who consume alcohol demonstrate less
radiographic progression than do male nondrinkers.
Objective. Alcohol consumption reduces the risk
of development of rheumatoid arthritis (RA) and significantly attenuates the development of erosive arthritis
in animal models. It remains unknown whether alcohol
consumption influences joint damage progression in
RA. This study was undertaken to compare the rates of
radiographic damage progression in alcohol drinkers
and nondrinkers in a large prospective cohort of patients with RA.
Methods. All patients in the population-based
Swiss Clinical Quality Management in RA registry
database with at least 2 sequential radiographs were
included. Joint erosions were assessed in 38 joints in the
hands and feet using a validated scoring method. The
rate of progression of erosions was analyzed using
multivariate regression models for longitudinal data
and was adjusted for potential confounders.
Results. The study included 2,908 patients with
RA with a mean of 4 sequential radiographs and 3.9
years of followup. A trend toward reduced radiographic
progression existed in drinkers compared with nondrinkers, with a mean rate of erosive progression of
Although the cause of rheumatoid arthritis (RA)
remains unknown, environmental risk factors are
thought to be important in its pathogenesis, with smoking representing the best-established risk factor (1). The
rate of radiographic progression of joint damage can be
used as a proxy measure for RA severity, representing
cumulative disease activity for an individual patient.
Many studies have demonstrated that radiographic joint
damage is associated with long-term disability (2,3), loss
of employment status (4), and social security disability
status (5). Despite the plethora of new and effective
therapies for RA, remission is not achieved in many
patients and there are ongoing signs of joint destruction.
A better understanding of the genetic and environmental risk factors is therefore essential for effective management.
In addition to smoking, numerous environmental
risk factors have been cited that may influence the
susceptibility for developing RA, including alcohol, cof-
Drs. Gabay and Finckh’s work was supported by the Swiss
National Science Foundation (grants 320000-119728 and 3200B0120639, respectively). The Swiss Clinical Quality Management Project
in Rheumatoid Arthritis is supported by Abbott, Bristol-Myers Squibb,
Essex Chemie, Roche, Wyeth, and the Swiss health authorities.
1
M. J. Nissen, MBBS, FRACP, C. Gabay, MD, A. Finckh,
MD, MS: University Hospital of Geneva, Geneva, Switzerland; 2A.
Scherer, PhD: University of Zurich, Zurich, Switzerland.
Dr. Gabay has received consulting fees, speaking fees, and/or
honoraria from Abbott, Essex, Wyeth, Roche, and Bristol-Myers
Squibb (less than $10,000 each).
Address correspondence and reprint requests to M. J. Nissen,
MBBS, FRACP, Division of Rheumatology, Department of Internal
Medicine, University Hospital of Geneva, 26 Avenue Beau-Séjour,
1211 Geneva 14, Switzerland (e-mail: Michael.J.Nissen@hcuge.ch); or
to A. Finckh, MD, MS: University Hospital of Geneva, 26 Avenue
Beau-Séjour, 1211 Geneva 14, Switzerland (e-mail: axel.finckh@
hcuge.ch).
Submitted for publication October 29, 2009; accepted in
revised form January 26, 2010.
1265
1266
NISSEN ET AL
fee, tea, oral contraceptive use, and socioeconomic
status, with varying levels of evidence. A recent study
demonstrated a protective effect of alcohol consumption
on the risk of developing RA, with a 40–50% reduction
in risk for the highest consumers (6), although some
smaller studies, either exclusively in women or with
alcohol consumption as a secondary outcome, found no
association between alcohol and RA onset (7,8). In
murine collagen-induced arthritis, the development of
erosive arthritis is almost totally abolished in mice
exposed to low levels of alcohol on a daily basis (9).
Nevertheless, it remains unknown whether alcohol influences disease severity or disease progression in established RA. The aim of this study was to assess the
influence of alcohol consumption on disease progression
in a large prospective cohort of patients with RA.
PATIENTS AND METHODS
Study population. The Swiss Clinical Quality Management (SCQM) project for RA is a longitudinal populationbased cohort of RA patients. Currently, more than two-thirds
of practicing rheumatologists in Switzerland are contributing
patients to the database. The SCQM database collects information on sociodemographic factors, lifestyle characteristics
(including alcohol consumption), antirheumatic therapies, disease activity, and radiographic damage at least annually. All
patients provided written informed consent prior to inclusion
in the database.
Study design. We conducted a longitudinal observational study of a population-based cohort of patients with RA.
The analysis included data collected between March 1996 and
February 2009. All patients in the database who met the
inclusion criteria of a confirmed diagnosis of RA by a rheumatologist, known alcohol consumption status, and at least 2
consecutive sets of radiographs of the hands and feet were
included. Patients were excluded if their alcohol status was
unknown or if followup radiographs were missing.
Outcome variables. The primary outcome of the study
was the progression of radiographic joint damage, as measured
by changes from baseline in radiographic damage scores.
Radiographic damage was assessed prospectively by a single
evaluator who was blinded with regard to clinical information;
a validated scoring system (the Ratingen score) was used (10).
This technique of radiologic scoring was chosen because it is
sensitive to change and is less susceptible to the ceiling effects
seen in advanced disease because of a true ordinal rating
system (11). The Ratingen scoring method has excellent reliability, with an intraclass correlation coefficient (ICC) for
intrarater reliability of 0.8–0.9 and an ICC for interrater
reliability of 0.7–0.9 (10,12). The minimal detectable radiographic change for this method has been determined to be
3.3% of the maximum score (10). For our study assessor, the
intrarater reliability was good, with an ICC of 0.94 for a
cross-sectional assessment and an ICC of 0.71 for change
scores.
A secondary outcome of the study was the progression
of functional disability, measured as change from baseline in
the Health Assessment Questionnaire (HAQ) disability index
(13). The HAQ score ranges from 0 to 3, where 3 represents
the maximum possible disability. This score has been demonstrated to predict work disability (14), medical expenditure
(15), and mortality (16).
Exposure variable and predictors. All patients were
categorized as drinkers or nondrinkers of alcoholic beverages,
based on the self-reported drinking status in the patient
questionnaire. Patients who discontinued drinking alcohol and
those who started drinking during the observation period were
categorized as drinkers. In order to explore a potential doseresponse effect of drinking, we further stratified drinkers as
occasional drinkers, daily drinkers (consumption of alcoholic
beverages on 1 occasion per day), and heavy drinkers (consumption of alcoholic beverages on several occasions per day).
Alcohol drinkers who changed their category of consumption
during the observation period were classified into the higher
category. Other important predictors of disease progression in
RA, such as disease activity measures, self-assessed symptom
questionnaires, various disease characteristics, and demographic characteristics, were extracted from the database and
included in the analyses. We determined the dominant antirheumatic treatment regimen used during the time span between consecutive radiographic assessments and used this
variable to control for the analysis of disease-modifying antirheumatic drug (DMARD) and biologic agent use. The dominant antirheumatic treatment was defined as the regimen used
for ⬎50% of the observation period.
Statistical analysis. Based on previous studies with this
cohort (17,18), we estimated that a sample size of 100 patients
per group would provide 90% power with an alpha error of less
than 0.05 to detect a 2-sided difference of at least 1 Ratingen
score unit (0.5% of the maximum score) in radiographic
damage progression per year. Differences in baseline disease
characteristics between the groups were compared using Student’s t-test for normally distributed variables, Wilcoxon’s rank
sum test for non-normally distributed continuous variables or
categorical variables, and Pearson’s chi-square test for dichotomous variables. Less than 5% of covariates were sporadically
missing. To minimize potential bias, we used the population
average of the respective covariates as a substitute.
Confounding was a concern in this study, since it is
possible that RA patients who regularly consume alcohol differ
from patients who do not drink alcohol with regard to important disease characteristics. Given that these differences could
substantially influence disease progression, we used multivariate adjustments to correct for such confounding effects.
Radiographic damage progression and functional disability
evolution were analyzed using generalized mixed models for
longitudinal data (19). We verified that the multivariate normal assumptions for longitudinal models were satisfied and
examined whether time as a linear trend or as a polynomial
function best fit the data. We adjusted the analysis for differences in baseline disease characteristics. Rheumatoid factor
(RF), age, sex, education level, Disease Activity Score in 28
joints (DAS28) (20), HAQ status, DMARD therapy, and
corticosteroid use at baseline were considered to be a priori
confounders and were entered into the model. We tested other
covariates using a backwards stepwise selection approach. The
estimated rate of radiographic progression at baseline was
EFFECT OF ALCOHOL ON RADIOGRAPHIC PROGRESSION IN RA
Table 1.
1267
Baseline characteristics of the patients with RA*
Age, years
Sex, % male
RF positivity, %
Education level, mean (IQR) years
Smokers, %
DAS28
HAQ score
Disease duration, mean (IQR) years
Erosion score, mean (IQR)
Erosive progression, mean (IQR)
Methotrexate, %§
Leflunomide, %§
Biologic therapy, %¶
Low-dose corticosteroids, %
Nondrinkers
(n ⫽ 1,084)
Alcohol drinkers
(n ⫽ 1,824)†
P‡
55.7 (54.9–56.5)
12 (10–14)
73.2 (70.5–75.9)
12 (9–12)
20.6 (18.2–23.1)
4.6 (4.5–4.7)
1.30 (1.25–1.34)
4.8 (1.0–12.1)
3.4 (0.9–13.1)
1.0 (0.3–2.4)
60.8 (57.8–63.7)
13.7 (11.7–15.8)
17.0 (14.8–19.3)
53.1 (50.1–56.1)
53.9 (53.3–54.5)
32 (30–34)
71.0 (68.9–73.1)
12 (12–12)
30.3 (28.2–32.5)
4.3 (4.2–4.3)
1.00 (0.96–1.03)
3.8 (0.9–11.6)
2.7 (0.8–9.3)
1.0 (0.3–2.2)
60.7 (58.4–62.9)
11.2 (9.8–12.8)
17.9 (16.2–19.8)
46.1 (43.8–48.4)
⬍0.001
⬍0.001
0.192
⬍0.001
⬍0.001
⬍0.001
⬍0.001
0.008
0.006
0.17
0.96
0.054
0.514
⬍0.001
* Except where indicated otherwise, values are the median (95% confidence interval). RA ⫽ rheumatoid
arthritis; RF ⫽ rheumatoid factor; IQR ⫽ interquartile range; DAS28 ⫽ Disease Activity Score in 28
joints; HAQ ⫽ Health Assessment Questionnaire; erosion score ⫽ percentage of the maximum possible
Ratingen damage score.
† Alcohol drinkers included occasional, daily, and heavy drinkers.
‡ By Wilcoxon’s rank sum test for non-normally distributed variables, Student’s t-test for normally
distributed continuous variables, and the chi-square test for dichotomous variables.
§ Disease-modifying agent use either as monotherapy or in combination with other agents.
¶ Use of any tumor necrosis factor inhibitor or rituximab.
calculated, since this is one of the strongest predictors of future
radiographic progression (21).
The final model was adjusted for differences in baseline damage scores, DAS28, functional disability (as measured
by the HAQ), presence of RF, sex, age, disease duration,
tobacco smoking, education level, and medications (including
DMARDs, biologic agents, and corticosteroids). Point estimates of the regression model at every year for the median
duration of followup were used to produce the graphs showing
the results. We considered the possibility of a dose response by
alcohol intake by classifying the alcohol exposure variable into
4 categories (none, occasional, daily, and heavy [several drinks
per day]), according to the categories on the patient questionnaire. We further investigated whether effect modification of
alcohol existed in various subgroups, such as those classified by
sex, RF status, smoking status, anti–cyclic citrullinated peptide
(anti-CCP) status (present, absent, or missing), or therapy with
biologic agents. All statistical tests were 2-sided and were
evaluated at the 0.05 significance level. Statistical analysis was
performed with Stata, version 9.2 for Windows (Stata Statistical Software).
RESULTS
Patient characteristics. Of the 4,834 patients with
RA in the SCQM registry, a total of 2,908 with a median
of 4 sequential radiographs and 3.9 years of followup
met the study inclusion criteria. Excluded patients were
missing either followup radiographs (n ⫽ 1,774), alcohol
consumption status (n ⫽ 149), or both (n ⫽ 3). Because
missing radiographic followup was related to recent
enrollment in the database (since excluded patients
enrolled, on average, 3.3 years later than included
patients [P ⬍ 0.0001]), we assumed absent followup to
be missing at random.
In this RA population, 1,084 patients (37%)
reported no alcohol consumption and 1,824 patients
(63%) reported at least some consumption of alcohol.
The alcohol drinkers included more male patients than
the nondrinkers, were younger, included a greater percentage of smokers, and had shorter disease durations,
lower DAS28 scores, and lower HAQ scores, with
consequently less joint erosion at baseline (Table 1). The
median estimated erosive progression at baseline was,
however, similar between drinkers (1.01 [interquartile
range 0.31–2.24]) and nondrinkers (1.04 [interquartile
range 0.32–2.40]). Among the drinkers, 1,486 (81.5%)
were occasional drinkers, 272 (14.9%) were daily drinkers, and 57 (3.1%) were heavy drinkers. Nine of the
2,908 patients (0.3%) indicated that they drank alcohol,
but did not specify their intake category and were
therefore excluded from the dose-effect analyses. Four
patients changed their drinking classification during
followup, with 2 patients reclassifying themselves as
drinkers and 2 patients becoming nondrinkers. These
patients were considered to be drinkers in the analyses.
Other important risk factors of disease progression, such
as RF seropositivity and type of antirheumatic therapy,
1268
Figure 1. Subgroup analysis of the different categories of alcohol
consumption based on the rate of radiographic joint damage progression (ERO) over time. Daily alcohol use refers to the consumption of
alcoholic beverages on one occasion per day, and heavy alcohol use
refers to the consumption of alcoholic beverages on several occasions
per day. The progression trajectories were adjusted for differences in
baseline damage scores, the Disease Activity Score in 28 joints,
functional disability (as measured by the Health Assessment Questionnaire), treatments (biologic agents, disease-modifying antirheumatic
drugs, and corticosteroids), presence of rheumatoid factor, sex, age,
disease duration, smoking status, and education level (the adjusted
model). The radiographic joint damage progression score represents
the percentage of the maximum possible Ratingen damage score and
corresponds to the average proportion of joint surface damage by
erosions. Values are the mean and 95% confidence interval (95% CI).
For clarity, the 95% CI for daily consumption is not shown and only
the upper 95% CI is shown for heavy consumption. Radiographic
progression at 1 year was 0.99% (95% CI 0.89–1.11) in the occasional
consumers and 0.92% (95% CI 0.70–1.13) in the daily consumers,
compared with 1.13% (95% CI 1.00–1.23) in the nondrinkers and
1.29% (95% CI 0.82–1.76) in the heavy consumers.
did not differ significantly between drinkers and nondrinkers. The use of oral corticosteroids was, however,
less common in the alcohol drinkers than in the nondrinkers (46.1% versus 53.1%; P ⬍ 0.001).
Radiographic damage progression. In the crude
analysis, the unadjusted evolution of radiographic damage was significantly less in the alcohol drinkers compared with the nondrinkers (P ⫽ 0.029). In the fully
adjusted model, there was a tendency toward reduced
radiographic progression in the drinkers, with radiographic damage at 1 year having progressed by a mean of
0.99% (95% confidence interval [95% CI] 0.89–1.09) in
the drinkers and by 1.13% (95% CI 1.01–1.26) in the
nondrinkers. The strongest predictors of radiographic
damage progression were disease duration, estimated
baseline radiographic damage, and RF.
Alcohol consumption displayed a J-shaped dose-
NISSEN ET AL
response effect, with a more favorable evolution in
occasional consumers and daily consumers compared
with nondrinkers, while disease in heavy drinkers
evolved less favorably. Radiographic progression at 1
year was 0.99% (95% CI 0.89–1.11) in the occasional
consumers and 0.92% (95% CI 0.70–1.13) in the daily
consumers, compared with 1.13% (95% CI 1.00–1.23) in
the nondrinkers and 1.29% (95% CI 0.82–1.76) in the
heavy consumers (Figure 1). Four years after inclusion,
radiographic progression was 3.85% in the heavy drinkers, 3.19% in the nondrinkers, 3.06% in the daily drinkers, and 2.96% in the occasional drinkers. Although the
differences between the 4 groups were not consistently
different at specific time points, using direct pairwise
comparisons, the longitudinal evolution of the group
curves were significantly different. The adjusted evolution of radiographic damage was significantly less in
occasional drinkers compared with nondrinkers (P ⫽
0.01) and in daily drinkers compared with nondrinkers
Figure 2. Subgroup analysis by sex of alcohol consumption based on
the rate of radiographic joint damage progression (ERO) over time.
The progression trajectories were adjusted for differences in baseline
damage scores, the Disease Activity Score in 28 joints, functional
disability (as measured by the Health Assessment Questionnaire),
treatments (biologic agents, disease-modifying antirheumatic drugs,
and corticosteroids), presence of rheumatoid factor, sex, age, disease
duration, smoking status, and education level (the adjusted model).
The radiographic joint damage progression score represents the
percentage of the maximum possible Ratingen damage score and
corresponds to the average proportion of joint surface damage by
erosions. Values are the mean and 95% confidence interval (95% CI).
For clarity, the 95% CI is shown for men only. Radiographic progression at 1 year was 0.86% (95% CI 0.70–1.03) in male drinkers and
1.35% (95% CI 1.02–1.67) in male nondrinkers (P ⫽ 0.007), an effect
which was not evident between female drinkers and nondrinkers
(1.04% [95% CI 0.92–1.15] versus 1.10% [95% CI 0.96–1.23], P ⫽
0.49).
EFFECT OF ALCOHOL ON RADIOGRAPHIC PROGRESSION IN RA
1269
reach statistical significance (P ⫽ 0.18) (Figure 3). There
was no significant effect modification in HAQ scores by
the quantity of alcohol consumption, sex, RF positivity,
or the use of biologic agents. The strongest predictors of
the progression of functional disability were high baseline HAQ score, female sex, RF positivity, and lower
education levels.
DISCUSSION
Figure 3. Progression of functional disability, as measured by the
Health Assessment Questionnaire (HAQ) score, over time according
to alcohol consumption. The progression trajectories were adjusted for
differences in baseline damage scores, the Disease Activity Score in 28
joints, functional disability (as measured by the HAQ), treatments
(biologic agents, disease-modifying antirheumatic drugs, and corticosteroids), presence of rheumatoid factor, sex, age, disease duration,
smoking status, and education level (the adjusted model). Values are
the mean and 95% confidence interval (95% CI). There was a trend
toward a different evolution of the 2 curves (P ⫽ 0.147), and at 5 years,
the increase in HAQ score was 0.36 (95% CI 0.32–0.41) in the drinkers
and 0.41 (95% CI 0.35–0.46) in the nondrinkers (P ⫽ 0.18).
(P ⫽ 0.001), while the radiographic evolution was significantly worse in heavy drinkers compared with occasional and daily drinkers (P ⫽ 0.0001).
Moreover, we found evidence of effect modification by sex (P ⫽ 0.05). Men who drank alcohol demonstrated a more pronounced reduction in radiographic
progression compared with men who did not drink
alcohol (0.86% [95% CI 0.70–1.03] versus 1.35% [95%
CI 1.02–1.67], P ⫽ 0.007) at 1 year, an effect which was
less evident in women (1.04% [95% CI 0.92–1.15] versus
1.10% [95% CI 0.96–1.23], P ⫽ 0.49) (Figure 2). No
effect modification existed with RF positivity (P ⫽ 0.62),
smoking status (P ⫽ 0.25), or use of biologic agents (P ⫽
0.13).
Progression of functional disability. To examine
the consistency of the radiographic data, we repeated
the analysis with the HAQ score as the outcome. Patients had a mean of 5.7 sequential HAQ assessments
during the observation period. As with the radiographic
data, there was a more favorable evolution in the
drinkers, with an increase in HAQ scores at 5 years of
0.36 (95% CI 0.32–0.41) in the drinkers and 0.41 (95%
CI 0.35–0.46) in the nondrinkers, although this did not
In this large observational study, we found a
trend toward a reduction in the progression of radiographic damage in alcohol drinkers, most specifically in
those with low to moderate consumption. The evolution
of functional capacity revealed a similar trend, although
it did not reach significance. We observed an unexpected
effect modification by sex, with a highly significant
reduction in radiographic progression in male drinkers.
Overall, this suggests that in addition to its role in the
development of RA, alcohol may also be involved in the
evolution of the erosive process. To our knowledge, this
is the first study to explore the effect of alcohol consumption on the progression of joint damage.
A recent study examined the effect of ethanol in
type II collagen–induced arthritis (9). The development
of an erosive arthritis was almost completely abolished
in the exposed mice, without any sign of toxic effects on
the liver. The antiinflammatory and antidestructive
properties of ethanol were mediated by significant reductions in interleukin-6 (IL-6), macrophage inflammatory protein 1␣, tumor necrosis factor ␣ (TNF␣), NF-␬B
nuclear translocation, down-regulation of leukocyte migration, and up-regulation of IL-10 production.
The chronic abuse of alcohol has been clearly
shown to cause immunosuppression, as well as an increase in overall morbidity and mortality (22). Subjects
who abuse alcohol show elevated levels of the proinflammatory cytokines TNF␣, IL-1, and IL-6 (23). However,
long-term intake of low to moderate amounts of alcohol
has been shown to reduce levels of TNF␣ (24,25), IL-1
(24), IL-6 (26,27), C-reactive protein (CRP) (26,28,29),
and NF-␬B activation (30,31) and to increase levels of
the antiinflammatory cytokine IL-10 (23,32,33).
The protective effect of alcohol consumption on
radiographic progression observed in men but not in
women may be partially explained by sex differences in
RA severity. A multinational cohort including ⬎6,000
RA patients demonstrated more active disease (in terms
of the DAS28), increased functional impairment (as
measured by the HAQ score), less remission, and more
erosion in female patients (34). Nevertheless, several
1270
other authors have demonstrated no sex differences in
terms of radiographic outcomes (14,35). Moderate alcohol consumption also appears to have a greater influence on systemic markers of inflammation, such as CRP
and leukocyte count, in men than in women (29).
Another hypothesis for the observed effect modification
of alcohol by sex could be related to the alcohol dose. In
general, men consume alcohol more regularly and in
greater quantities than women (36). In this population,
male drinkers were twice as likely to consume alcohol
daily (27% of males compared with 14% of females),
which is the category in which the beneficial effect of
alcohol on radiographic progression was most pronounced.
Although the effect size is relatively small over a
short timeframe, the clinical importance may well be of
greater significance over the course of a lifetime in a
chronic disease such as RA. Differences of this magnitude are probably clinically meaningful for men over the
long term, but not necessarily for women. Given our
findings, it would appear prudent to include alcohol
consumption in future studies investigating radiographic
progression in RA patients, particularly when analyzing
the effect of sex.
Our study does have several limitations. Approximately one-third of the patients in the registry did not
have sequential radiographic followup and were excluded. Our results could potentially be biased if missing
radiographic followup was associated with both alcohol
consumption and more severe radiographic progression.
There are a number of reasons why we think that the
results are unlikely to be due to selection bias. First, the
predominant reason for missing followup radiographs
was recent enrollment in the database with insufficient
time for subsequent radiographs. Second, there are no
data to suggest that missing radiographic followup is
related to more severe disease progression. In fact, the
excluded patients in this analysis had baseline characteristics that were very similar to those of the included
patients, with no differences in terms of estimated
baseline radiographic damage (P ⫽ 0.99), sex (P ⫽ 0.86),
or RF status (P ⫽ 0.41), and only minor, clinically
irrelevant differences in age (56.1 versus 54.4 years),
DAS28 scores (4.31 versus 4.47), and HAQ scores (1.25
versus 1.11).
We performed a sensitivity analysis comparing
the classification of occasional drinkers as drinkers or
nondrinkers and consequently classified this subgroup as
drinkers. Inclusion and followup in the SCQM database
are unrelated to alcohol consumption. Enrollment in the
database is determined by both physician and treatment
NISSEN ET AL
choices. Enrolled patients tend to have more severe
disease and receive more biologic therapies than RA
patients in the general population (37). It is therefore
highly unlikely that alcohol drinkers or nondrinkers were
differently enrolled. However, one must keep in mind
that these results relate to a single population of predominantly white patients in Switzerland and may not
necessarily be directly extrapolated to other populations.
We used self-reported alcohol consumption status, which may be prone to underreporting and misclassification. While patients may have underreported their
alcohol consumption to “please” their physicians, it is
very unlikely that alcohol consumption was differentially
misclassified by levels of disease severity. Recall bias is
unlikely to have been a concern, since we targeted the
overall pattern of alcohol consumption rather than the
exact amount over a predefined period. Another potential problem is that RA patients may change their level
or pattern alcohol consumption over time; however, only
a few participants in our cohort changed their alcohol
drinking status during followup. In a Scandinavian cohort, alcohol consumption by RA patients with a disease
duration of ⬍6 months did not differ from that reported
by patients with a longer disease duration (6).
Another potential bias may arise in RA patients
treated with potentially hepatotoxic DMARDs or nonsteroidal antiinflammatory drugs (NSAIDs), who may
be advised to stop or reduce their alcohol consumption.
While this is a theoretical concern, it has been demonstrated that no significant differences exist in alcohol
consumption between RA patients taking either methotrexate (MTX) or NSAIDs and those who were not (6).
In addition, in a UK study of 200 RA patients who were
given clear advice to cease alcohol consumption prior to
the introduction of a DMARD, the vast majority of
patients treated with MTX continued to drink alcohol
(38). In our study, we investigated the pattern of
DMARD use between drinkers and nondrinkers and did
not find any significant differences, which is consistent
with the results of previous studies. However, the differences in transaminase levels with regard to varying levels
of alcohol consumption have yet to be analyzed. Patients
taking MTX who drank alcohol did not discontinue
MTX more frequently than nondrinkers (P ⫽ 0.64 by
Cox proportional hazards model), suggesting that moderate alcohol consumption did not result in significantly
higher elevations of transaminase levels compared with
nondrinkers who were taking MTX.
The effect of certain environmental risk factors,
most specifically smoking, appears particularly strong in
the setting of anti-CCP–positive RA. Unfortunately,
EFFECT OF ALCOHOL ON RADIOGRAPHIC PROGRESSION IN RA
anti-CCP status was available in only 24% of the patients
in our study and could therefore be an unmeasured
confounder. In this subset, the proportion of alcohol
drinkers who were anti-CCP positive was very similar to
the proportion of the nondrinkers who were anti-CCP
positive (58.5% and 57.9% respectively, P ⫽ 0.881).
Moreover, we found no evidence of effect modification
by anti-CCP status (positive, negative, or missing).
One of the strengths of our analysis is the use of
a large, prospective, population-based cohort of RA
patients. Quantification of radiographic status was performed using well-validated and reproducible methods,
with high intrarater and interrater correlations. The
statistical power of our study was sufficient to detect
small differences in rates of radiographic progression.
With the use of a longitudinal regression analysis, we
adjusted for a large number of potential confounders,
such as the use of various therapeutic agents, RF,
smoking, and socioeconomic status.
In conclusion, a trend toward reduced radiographic progression was observed in drinkers compared
with nondrinkers, particularly in the occasional and daily
consumers. Men who drank alcohol demonstrated a
more pronounced reduction in radiographic progression
compared with men who did not drink, an effect which
was not seen in women. Although the effect size is
relatively small over a short timeframe, the clinical
importance may well be of greater significance over the
course of a lifetime, particularly in male RA patients.
While the careful surveillance of alcohol consumption,
particularly in combination with drugs such as NSAIDs
and DMARDs, remains an essential component of good
management, perhaps the universal recommendation to
cease low to moderate alcohol consumption may be
questioned for selected RA patients. Further research is
required to better understand the impact of alcohol
consumption on RA in terms of the type of alcohol,
drinking pattern, volume, drug interactions, and the
ethnicity of the population.
ACKNOWLEDGMENTS
The authors are grateful to all of the physicians who
contributed valuable time to the enrollment and followup of
this group of patients in the SCQM, as well as to all of the RA
patients in the database, without whom this type of study
would not have been possible.
AUTHOR CONTRIBUTIONS
All authors were involved in drafting the article or revising it
critically for important intellectual content, and all authors approved
1271
the final version to be published. Dr. Nissen had full access to all of the
data in the study and takes responsibility for the integrity of the data
and the accuracy of the data analysis.
Study conception and design. Nissen, Gabay, Finckh.
Acquisition of data. Nissen, Scherer.
Analysis and interpretation of data. Nissen, Finckh.
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