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The progression of erosion and joint space narrowing scores in rheumatoid arthritis during the first twenty-five years of disease.

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660
THE PROGRESSION OF EROSION AND JOINT SPACE
NARROWING SCORES IN RHEUMATOID ARTHRITIS
DURING THE FIRST TWENTY-FIVE YEARS OF
DISEASE
JOHN T. SHARP, FREDERICK WOLFE, DONALD M. MITCHELL, and DANIEL A. BLOCH
Erosions and cartilage destruction are nearly
universal features in peripheral joints that have been
chronically affected by rheumatoid arthritis. Scoring
methods to measure the extent of these abnormalities in
hands and wrists have been developed and have been
thoroughly tested in several studies to establish their
reproducibility. In this study, we utilized one of these
scoring methods to examine the progression of radiologic damage as related to duration of disease. Two
hundred ninety-two patients from 3 different participating centers in the Arthritis, Rheumatism, and Aging
Medical Information System were included. Six hundred fifty films of the hands and wrists, obtained from
210 patients, were scored for erosions and joint space
narrowing. The average annual rate of progression of
the total radiologic score, which sums erosion and joint
space abnormalities and has a maximum possible score
of 314, was approximately 4 units per year over the first
From the University of Colorado School of Medicine,
Denver; The Joe and Betty Alpert Arthritis Center at Rose Medical
Center, Denver, Colorado; the University of Kansas School of
Medicine, Wichita; The Arthritis Center, Wichita, Kansas; and the
Divisions of ImmunologylRheumatologyand Biostatistics, Stanford
University School of Medicine, Stanford, California.
Supported in part by NIH grant AR-21393, and by clinical
research funds from Rose Medical Center.
John T. Sharp, MD: Professor of Medicine, University of
Colorado School of Medicine, and Director, The Joe and Betty
Alpert Arthritis Center at Rose Medical Center (current address:
Clinical Professor of Medicine, Emory University School of Medicine, Atlanta, Georgia); Frederick Wolfe, MD: Clinical Professor of
Medicine, University of Kansas School of Medicine, Wichita, and
Director, The Arthritis Center; Daniel A. Bloch, PhD: Senior
Research Associate, Stanford University School of Medicine.
Dr. Mitchell is deceased.
Address reprint requests to John T. Sharp, MD, 712 East
18th Street, Tifton, GA 31794.
Submitted for publication April 5 , 1990; accepted in revised
form December 31, 1990.
Arthritis and Rheumatism, Vol. 34, No. 6 (June 1991)
25 years after onset; this progression was more rapid in
the earlier years of disease and slightly slower in the
later years. Data were insufficient to accurately determine the progression rate in disease of more than 25
years duration.
Rheumatoid arthritis (RA) is a chronic inflammatory disease that frequently follows a course which
is continually progressive for many years. A number
of features have been proposed to measure its progression and outcome. One of these, radiologic assessment, measures the extent of bony erosions and loss of
articular cartilage. Several methods have been proposed to assess these features (1-12), and studies
comparing various methods have concluded that there
is strong agreement among different observers using
either the same or different techniques, and among the
scores assigned to the same set of radiographs by the
same observer using different methods (4,6,7,10-13).
These studies have established the reproducibility of
scoring radiologic abnormalities.
The present study utilized one of these scoring
methods (1 1) to determine the progression of radiologic abnormalities in approximately 100 consecutive
patients from each of 3 different centers. Radiologic
abnormalities were observed to develop at a nearly
steady rate between 3 and 25 years after onset of
disease. Although limitations were imposed on the
study by the discontinuous nature of the data, it is
unlikely that more complete data can be obtained.
METHODS
This multicenter study utilized data maintained in the
databanks of the Arthritis, Rheumatism, and Aging Medical
RADIOLOGIC PROGRESSION IN RA OVER 25 YEARS
Table 1. Number of patients and films, by patient location
No. with
2or
with
films
more
films
No. of
films
films per
patient
100 90 (90)
103 58 (56.3)
89 62 (69.7)
292 210(71.9)
67
57
39
163
199
270
181
650
2.2
4.7
2.9
3.1
80
77
49
206
76 (95)
50 (64.9)
48 (98)
174 (84.5)
63
49
31
143
180
245
153
578
2.4
4.9
3.2
3.3
20
26
40
86
14 (70)
8 (30.8)
14 (35)
36 (41.9)
4
8
8
20
19
25
28
72
1.4
3.1
2.0
2.0
No.
(14). The last 103 patients with a diagnosis of definite or
classic RA (15) were selected for this study.
The Wichita databank was begun in 1976 by entering
data on established and new patients from the practice of one
of the authors (FW). Laboratory and radiographic data were
obtained on patients as needed for clinical care. The first
consecutive 100 patients from this databank with a diagnosis
of definite or classic RA were chosen for the present study.
The first 100 consecutive patients admitted to the
Alpert Arthritis Center on or after January 1, 1975 with an
admitting diagnosis of RA were selected from the Denver
databank. The diagnosis in 11 patients was changed at the
time of hospital discharge or during the course of followup,
leaving 89 patients with definite or classic RA who were
included in this study.
During the study, efforts were made to reexamine
every living patient. The evaluation included a detailed joint
examination and general physical examination. Laboratory
data obtained included a complete blood cell count, erythrocyte sedimentation rate, rheumatoid factor titer by latex
fixation, and fluorescent antinuclear antibody titer. A disability index was calculated from items on the Health
Assessment Questionnaire (16). Patients who could not
come to the centers were sent questionnaires or interviewed
by telephone and were asked to have radiography and
laboratory tests performed by their family physicians.
All patients were successfully traced. Eighty-six of
the 292 had died. All the known previous hand and wrist
films were collected, and new films were obtained when
possible. A total of 650 films were obtained from 210 (72%)
of the 292 patients (Table I ) . Of those with films, there was
an average of 3.1 films per person, and 163 had 2 or more
films. Films were obtained on 48 of 49 living patients in the
Denver group (98%), but only 14 of the 40 who had died
(35%). The Kansas center obtained films from 90% of their
Average
No. (%)
no. of
All patients
Kansas
Saskatoon
Denver
Total
Patient still
living at
time of
study
Kansas
Saskatoon
Denver
Total
Patients
deceased
at time
of study
Kansas
Saskatoon
Denver
Total
66 1
Information System, from the University of Saskatchewan,
Saskatoon, Canada, The Arthritis Center of Wichita, Kansas, and The Joe and Betty Alpert Arthritis Center, Rose
Medical Center, Denver, Colorado.
One thousand two hundred five patients over the age
of 16 with a clinical diagnosis of RA, who were enrolled in a
followup program at the University of Saskatchewan between 1966 and 1974, constitute the Saskatoon databank
Table 2. Characteristics of the study population, by patient location*
~~
Kansas
No. of patients
Age at first visit, years
Age at last visit, years
Age at disease onset, years
% female
Disease duration at first visit, years
Disability index at first visit, 0-3 scale
Nodules, % ever hadt
Morning stiffness, hours
ESR, mm/hour$
Hemoglobin, gm/dl
RF, log titer9
52.4
60.4
44.3
8.0
1.21
2.10
36.5
12.7
743
100
t 1.42
t 1.37
t 1.39
72
t 0.907
t 0.106
45
2 0.252
t 1.98
2 0.127
t 124
Saskatoon
Denver
103
89
55.9 t 1.44
65.1 t 1.40
45.5 t 1.44
66
10.4 2 0.959
1.35 t 0.150
34
1.97 ? 0.347
49.0 t 2.40
12.9 t 0.159
818 t 163
53.4
62.3
43.7
* 1.57
?
?
1.41
1.53
63
9.7 t 1.12
1.09 t 0.102
55
I .47 ? 0.133
47.0 t 2.64
12.9 ? 0.157
2,181 t 266
292
53.8
62.5
44.4
67
9.4
1.20
45
1.82
44.1
12.9
1,317
* Unless otherwise indicated, values are the mean t SEM. Values for morning stiffness, erythrocyte
sedimentation rate (ESR), and hemoglobin were averaged over all observations.
I A patient was considered to have nodules if a nodule was recorded as present at any time during the
course of observation. For comparison of nodule frequency across groups, 2 = 9.022, degrees of
freedom [dfl = 2, P = 0.01 1.
$ The average ESR values were significantly different across groups (one-way F statistic = 8.002, df
= 2,285, P < 0.001).
0 The average titers of rheumatoid factor (RF; by latex fixation) were significantly different across
groups (one-way F statistic = 16.350, df = 2,257, P < 0,001).
SHARP ET AL
662
Table 3. Characteristics of patients who were still living at the time of the study and patients who
were deceased at the time of the study, according to availability of films*
No. of patients
Age at first visit, yearst
Age at last visit, yearst
Age at disease onset, yearst
% female
Disease duration at first
visit, years$
Disease duration at last visit,
years
Disease duration at first film,
years§
Disease duration at last film,
years
Radiologic progression rate,
units/years§
Disability index at first visit,
0-3 scale
Nodules, % ever had
Morning stiffness, hours
ESR, mm/hourt
Hemoglobin. gm/dl$
RF, 10gtiter -
Living
patients
with films
Living
patients
without films
Deceased
patients
with films
Deceased
patients
without films
174
48.9 2 1.05
58.8 2 1.05
41.2 -t 0.999
71.7
7.5 2 0.688
32
54.0 t 2.72
62.5 rt 2.59
43.8 t 2.74
56.3
10.2 t 1.62
36
62.0 2 1.29
68.6 t 1.39
49.7 2 2.20
58.3
12.2 ? 1.75
50
65.2 2 1.69
70.8 t 1.63
52.1 t 2.08
64.0
13.1 t 1.61
17.5 t 0.707
18.7 2 1.55
18.9
1.82
18.7 t 1.61
?
9.6 2 0.773
13.3 2 1.73
16.2 t 0.729
15.7 t 1.89
4.71 t 0.424
7.90 2 1.80
1.11 t 0.073
0.762 t 0.206
47.7
1.76 t 0.137
37.8 2 1.48
13.1 t 0.101
1,271 f 176
40.6
1.32 t 0.239
44.0 t 4.17
13.1 rt 0.299
1,321 t 280
1.77
0.207
2.00 t 0.277
44.4
2.85 t 0.706
51.7 t 3.88
12.6 ? 0.224
1,811 ? 347
40.0
1.63 t 0.366
60.3 t 4.11
12.2 t 0.225
1,141 t 248
f
* P values for comparisons of living patients who had films with living patients who did not have films
and of deceased patients who had films with deceased patients who did not have films varied between
0.057 and 0.943, with only 2 values CO.10. The 2-sample t-test was used to compare means of
continuous variables, and the chi-square test was used to compare dichotomous variables. Unless
otherwise indicated, values are the mean t SEM. See Table 2 for additional explanations and
definitions.
t P < 0.001, all living patients versus all deceased patients.
j: 0.001 < P < 0.01, all living patients versus all deceased patients.
$ 0.01 < P < 0.05, all living patients versus all deceased patients.
patients, including 76 of the 80 who were living (95%) and 14
of the 20 who had died (70%). The largest number of
available films per patient was from the Saskatoon group.
For scoring of radiologic changes, individual paTable 4. Progression of radiologic scores in patients who had 2 or
more films, by disease duration
Disease duration,
mean (range)
years*
No. of
patients
2.0 (0.91-3.3)
6.1 (5.05-7.29)
10.0 (8.81-11.15)
14.0 (12.90-14.82)
18.1 (17.33-18.83)
22.8 (21.8624.36)
23
31
22
12
9
6
Radiologic
progression rate,
mean t SEM
unitdyeart
9.076
5.270
6.291
10.109
5.089
2.819
2
3.275
t 1.240
t 2.214
t 2.124
2 2.046
t 0.821
* Patients were selected who had 2 or more films in 4-year intervals
between 0 and 20 years of disease, or between 20 and 25 years of
disease. Ranges given are the actual disease durations.
t The mean radiologic progression rate was determined from the
rates of progression in all patients in the duration interval who had
2 or more films, using method I , as described in Methods.
tient’s films were identified in sets. Within sets, the sequence
of films was blinded, using random number tables to assign a
label A, B , C, . . . etc. For example, a patient with 3 films
would be equally likely to have the first film labeled A, B, or
C. All radiographs were scored by one of the authors (JTS)
for extent of erosions and joint space narrowing, using a
modification of the method he originally described, which
has been thoroughly tested ( I , 11). Films from Kansas were
also scored by FW, and films from Saskatoon by DMM.
Correlation coefficients were 0.953 (n = 122) between FW
and JTS and 0.948 (n = 229) between DMM and JTS. Since
JTS was the only one who read all films, the scores used in
the studies reported here are those he assigned.
Total radiologic scores were the sum of erosion
scores for 34 joints and joint space narrowing scores for 36
joints (1 1). If surgery had been performed during the interval
between 2 films, the score of the film obtained before the
surgery was assigned to each joint that was affected by the
operation, so that progression rates would not artifactually
retrogress.
Data on 142 variables collected on patients in each
center were extracted into special files and merged. Analysis
was carried out using Medlog (17) and SAS (18) software
programs.
RADIOLOGIC PROGRESSION IN RA OVER 25 YEARS
Table 5. Progression of radiologic scores in films taken early in the
disease course and films taken late in the disease course, in the same
patients*
First film
Last film
No. of
patients
Disease duration,
mean years
Radiologic
progression rate,
mean t SEM
units/year
62
62
4.057
14.206
4.1 10 t 0.898
4.218 k 0.474
* All patients were selected who (a) had their first film within 10
years after disease onset, (b) had their last film more than 10 years
after onset and more than 1 1 months after the first film, and (c) had
the last film obtained after January I , 1984. The mean interval
between films was 10.2 years (range 1.5-14.5 years). Radiologic
progression rates shown in this table were calculated by method 2,
i.e., progression rate = score + disease duration.
Three different methods of measuring the rate of
progression of radiologic abnormalities for each patient were
tested. Method 1 used the slope of radiologic scores for each
individual patient who had 2 or more films, by employing the
regression equation using radiologic scores as the dependent
variable and years from disease onset as the independent
variable. Method 2 calculated the progression rate by dividing the radiologic score by the duration of disease in years
for each film, and determined the mean for all films as that
individual’s progression rate. Method 3 took the difference
between the first and last radiologic scores and divided by
the difference in time in years. Methods 1 and 3 required that
the patient have 2 or more films, whereas every patient with
1 or more films was included in the rates determined by
method 2. Methods I and 3 were based on observed lime
between films, whereas method 2 relied on the patient’s own
report of the date of disease onset. Progression rates presented herein were determined by method 1 except where
otherwise indicated.
663
Table 7. Progression of radiologic scores in patients at each center, by disease duration
Disease
duration,
years
0.01-3
3-10
1C15
15-25
Mean radiologic progression rate, units/year*
Kansas
Saskatoon
8.628 (7)
6.829 (23)
2.932 (5)
3.144 (9)
3.827 (8)
5.174 (28)
5.953 (8)
2.560 (15)
Denver
2.164
8.270
2.768
5.348
(5)
(14)
(14)
(7)
* Determined by method I , as described in Methods. Values in
parentheses are the number of patients.
RESULTS
Patients from the 3 centers were comparable in
most important respects (Table 2). To assess the
potential bias created by incomplete radiologic data,
patients with radiographs available were compared
with those without. There were significant differences
with regard to age at first and last examination, age at
onset of disease, and duration of disease at first
examination. These differences are accounted for by
the greater proportion of deaths in the group without
films. When clinical and laboratory features of disease
were compared between living patients with films and
living patients without films, the living patients with
films were representative of all living patients and the
deceased patients with films were representative of all
deceased patients (Table 3). This suggests that our
assessment of the radiologic progression rate may be
Table 8. Ceiling scores at 5-year intervals for the first 25 years of
rheumatoid arthritis*
% of joints given ceiling scores,
mean 2 SEM
Table 6 . Progression of radiologic scores in the 29 patients who
had 5 or more films, all more than 1 year apart
Disease duration
at midpoint
between films,
mean
SEM
years
*
Film pair
Films
Films
Films
Films
I and
2 and
3 and
4 and
2
3
4
5
4.23
6.87
9.77
12.68
t 0.687
t 0.711
t 0.750
t 0.741
Radiologic
progression
rate, mean t
SEM units/
year*
4.554
5.368
7.231
5.017
2
0.192
t 0.172
t 0.318
5 0.281
* Radiologic progression rates shown in this table were calculated
by the following formula for each sequential pair of films (method 3):
progression rate =
radiologic score (second film) - radiologic score (first film)
time between films in years
Disease duration, mean
(range) years
2.7 (0-5)
7.6 (5-10)
12.3 (10-15)
17.2 (15-20)
22.3 (2C25)
3 1.7 (2548)
No. of
films
132
159
111
59
38
45
Erosion
score of 5
0.7
3.5
5.4
14.7
19.4
19.7
JSN
score of 4
Erosion
score of 5
and JSN
score of 4
t 0.243 0.05 2 0.047
t 0.593 0.7 2 0.189
1.05
2.45
t 3.99
t 3.67
4
2
0.3 t 0.135
2.1 2 0.330
1.5 k 0.336 3.4 0.591
2.5 2 0.684 8.5 t 1.36
3.6 t 1.45 11.2 C 2.20
3.8 t 0.976 11.5 2 2.16
* Ceiling scores are the highest scores used in the scoring system
(score of 5 for erosion, score of 4 for joint space narrowing [JSN]).
Percent ofjoints given ceiling scores were determined as the number
ofjoints scored 5 for erosions divided by the number ofjoints scored
for erosions, the number of joints scored 4 for JSN divided by the
number of joints scored for JSN, and the sum of joints scored 5 for
erosions and 4 for JSN divided by the sum of the number of joints
scored for erosions and those scored for JSN.
664
SHARP ET AL
centers, the possibility that this may have introduced
bias by causing overrepresentation of patients with
active and progressive disease was considered. To
assess this, we selected 62 patients who (a) had 2 or
more films, (b) had their first film within the first 10
years after onset of disease, (c) had their last film more
than 10 years after onset and at least 11 months after
the first film, and (d) had their last radiography performed after January 1, 1984, as part of the routine
fbllowup for this study. The progression rates for the
early films were not different from the late ones, as
determined by method 2 (Table 5).
Twenty-nine patients had 5 or more films, with
at least a I-year interval between each pair of films.
The rates of radiologic progression for each sequential
film pair were not significantly different (Table 6).
Progression rates were determined for each of
the centers separately, using longer intervals to allow
250
200
w 150
8
s:>a
p:
>;:
ii
100
50
0
10
20
30
40
50
160
60
DURATION OF DISEASE (years)
Figure 1. Total radiologic scores as a function of disease duration,
ih all patients for whom 2 or more films were available.
140
120
slightly underestimated because of the underrepresentation of those patients who died during the followup
period. However, deaths were not clustered in the
early years of disease, and in fact, the duration of
disease at last visit was similar for patients who had
died and those who were still living at the end of the
study. Therefore, no attempt was made to adjust
progression rates, due to the small correction that
would be required.
Using several methods, a significant change in
rates of progression of radiologic scores with increasing duration of disease was not detected. Progression
rates at 4-year intervals, determined by method 1,
varied substantially but did not show a trend, and
mean rates were not significantly different at different
durations (Table 4). In this analysis, 4-year intervals
were chosen as the shortest intervals that include a
meaningful number of patients in each interval who
had 2 or more films taken at least 11 months apart
within the interval.
Since films were obtained during the early years
of the study as part of routine patient care in all
w
100
U
0
5:
>.
80
a
g:
x
60
40
20
1
(n) = ## patients contributing
0
10
20
30
40
DURATION OF DISEASE (years)
50
Figure 2. Progression of radiologic scores as illustrated using the
averages of constrained cubics at increasing durations of disease.
RADIOLOGIC PROGRESSION IN RA OVER 25 YEARS
larger numbers of patients in each subset. N o trends or
consistent differences were observed (Table 7).
The possibility that a ceiling effect might have
occurred as a result of the scoring method was examined by tabulating the number of joints in each individual radiologic score that were assigned the highest
score for erosion and/or joint space narrowing. The
percentage of joints scored at the top of the scales
steadily increased with increasing duration of disease
(Table 8), indicating that a ceiling effect may have
accounted for part of the apparent decline in the rate of
progression of radiologic scores with increasing duration of disease.
The relationship of radiologic scores to duration
of disease was examined further by fitting several
models. The complexity of the task is illustrated in
Figure 1 , which plots radiologic scores against duration of disease for all patients who had 2 or more films.
It is evident that subjects were observed for varying
lengths of time at different durations of disease.
The first model-based method fitted a constrained cubic through patients’ data (86 patients had 3
or more data points), using the following constraints:
1) the model would pass through the origin, corresponding to a score of 0, at the onset of disease, and 2)
the cubic would be nondecreasing. These cubics,
which are averaged in Figure 2, suggest a gradually
decreasing rate up to approximately 25 years of disease. After this time, there were data on only 4
subjects.
The second method, based on fitting a quadratic
curve through each patient’s data, was chosen because
a preponderance of subjects would be expected to
have negative regression coefficients for the quadratic
term if the rate of progression of radiologic scores
were decreasing with increasing duration of disease.
This analysis demonstrated closely similar proportions
of subjects having positive and negative quadratic
regression coefficients.
One nonparametric method fitted a smooth
curve through the scatterplot of first-order differences
using moving averages. This method suggested a decreasing rate after approximately 25 years of disease,
but, using 25 bootstrap replicates, the variability of the
results was large.
In summary, the results of one modeling technique and a nonparametric analysis suggested a decreasing rate of radiologic progression after longer
durations of disease, though the data were not conclusive. Based on the data in Tables 4,5, and 6 and Figure
2, the mean rate of progression of radiologic scores is
665
approximately 4 units per year over the first 25 years
of disease, but the rate may be more rapid by as much
as twofold in the very early years and slower by
twofold in the later years. Data beyond 25 years
duration were too scanty to enable estimation of the
rate of progression.
DISCUSSION
Radiologic abnormalities in rheumatoid arthritis
accurately represent disease severity and progression.
Erosions and loss of cartilage are direct effects of the
disease process of RA. Scoring of radiologic abnormalities is reproducible (4,6,7,10-13), and these scores
correlate with the extent of deformities, limitation of
motion, and disability (1,19-21). The progression of
radiologic abnormalities correlates with the extent of
joint swelling during the interval between films (22),
the presence of nodules ( l ) , and laboratory abnormalities which reflect the severity of disease (1,9,19,2325). X-ray films represent a permanent record, and
objectivity in scoring is assured by assigning a random
and blinded sequence.
The rate of progression of radiologic abnormalities is very important in defining the “natural history”
of the disease and in determining the effectiveness of
therapeutic measures. Previous long-term, longitudinal studies on radiologic changes in the hands and
wrists were limited. Initially, Scott et al, in following
the cases of 88 patients with RA for 10 years, observed
no relation between the rate of radiologic progression
and the duration of disease (24). In another study of
patients at the same institution, however, total Larsen
scores (2,3) for 13 groups of joints (10 groups in
addition to fingers and wrists) demonstrated a weak
relationship between radiologic abnormality and duration of disease when analyzed by linear regression
(21): The rate ofjoint damage was negatively related to
the square root of disease duration (r = -0.44).
However, the number of cases was small, and 2
outliers may have accounted for an undue proportion
of the association. Subsequently, Scott and colleagues
demonstrated that radiologic progression decreased in
the later years when plotted as an absolute score, but
was linear when calculated as a percentage of maximum possible change (26), a result that would be
expected with a ceiling effect.
De Carvalho et a1 (27), who studied the sum of
Larsen scores on “all limb joints, the cervical spine
and the sacroiliac joints” and Larsen (28), who studied
hands and wrists, reported that radiologic scores in-
SHARP ET AL
creased at a steady rate when plotted against the
square root of duration of disease. However, de Carvalho and colleagues (29) demonstrated a high proportion of maximal scores in study patients with longer
disease duration, and Larsen and Thoen (28) recognized the possibility that a ceiling effect was responsible for the leveling off of the progression in the later
years.
Ideally, we would like to know the radiologic
scores at regular intervals from the onset of disease
through the remaining lifetime, for a sufficient number
of typical patients to define the mean progression rate
and the variability across patients. Unfortunately,
these data are not likely to ever be obtained. Some
patients do not receive care in the early years of their
arthritis. Many shift care between providers, and
others discontinue their visits to providers because
their disease has gone into remission or they have
become discouraged by poor response to treatment.
Other patients are lost to followup when they enter
nursing homes. There are no practices and very few
clinics that have been established long enough to have
followed patients for the 50 years or longer that would
be required to collect clinical data on a large group of
patients from disease onset to death. Films are not
obtained at regular intervals and may not be kept more
than a few years. Some drugs have been demonstrated
to slow the course of radiologic progression over the
short term, and these drugs are used regularly in
modern clinics for patients who appear to have progressive disease (30-34).
For these reasons, we have accepted the
premise that it is unlikely that complete data will be
obtained and have studied consecutive patients from 3
geographically disparate centers which represent different forms of practice. The rate of progression of
radiologic abnormalities was found to be minimally
influenced by the duration of disease, up to 25 years
from the time of onset. How firm is this conclusion?
Can we believe that RA (measured by radiologic
abnormality scores) progresses at a nearly steady rate
for the first 25 years across the “universe” of RA
patients, or must we have some reservations that the
sample in this study was not representative of RA in
the general population?
A number of factors that might influence the
analysis must be considered. Films were obtained on
84% of living patients from all centers and on more
than 94% from 2 of the centers (Table 1). Since there
were no apparent differences among the 3 centers in
the rates of radiologic progression (Table 7) and no
clinical or laboratory features were overrepresented in
patients without films (Table 3), we conclude that
factors influencing which living patients had films
obtained did not produce a large bias.
The problem is more serious with regard to
deceased patients, of whom only 41% had films available. Among deceased patients, those without films
were older at onset of disease and when first examined, but other differences were not significant. The
duration of illness at the time of the last followup and
the duration at the time the last film was obtained were
not appreciably different between those with and without films, whether living or- deceased. Therefore, it
seems reasonable to conclude that the deceased patients with films are representative of all deceased
patients and that the data are representative of rheumatoid arthritis in these 3 centers during the observation period.
Other investigators have emphasized that radiologic abnormalities are common in the first few years
of disease but have not undertaken longitudinal studies
comparing the rate of progression in the early period
with that in the subsequent years. The data presented
here are somewhat scanty with regard to the first 2
years of RA and do not enable firm conclusions to be
drawn regarding the progression rate in this early
phase of the disease. This caution is reinforced by the
observation that the graph of radiologic progression
drawn from the regression equation shows a positive
radiologic score at zero duration of disease. This effect
might result from a different slope during the first 2 or
3 years of illness or from a systematic error in determining the date of onset of disease.
The number of films obtained after 25 years of
disease is limited, and we have not attempted to draw
any conclusions about the progression of radiologic
abnormalities in this late period of illness. One would
expect that a ceiling effect might occur in the late stage
of disease. When scores for individual joints were
analyzed, the percentage that had reached the maximum score increased with greater duration of disease,
suggesting that a ceiling effect in the individual joint
scores could account for some of the gradual decrease
in the progression rate of radiologic scores shown in
Figure 2.
It should also be pointed out that individual
readers use the scoring system differently. JTS, who
read all the films in this study, is one of the more
conservative scorers among multiple readers who
scored a test set of films in a recent study (11). Films
read by a reader who regularly scores involved joints
RADIOLOGIC PROGRESSION IN RA OVER 25 YEARS
higher in the scale would s h o w a greater ceiling effect
in a group encompassing t h e wide time span a n d
extremes of severity represented in this study.
Although data from t h e first 3 years of disease
a n d after 25 years are scanty, t h e results shown in
Figure 2 suggest that progression of radiologic scores
over the first 25 years of RA is fairly constant, with an
average rate of increase of approximately 4 units per
year, perhaps somewhat more rapid in the very early
years a n d slowing to a b o u t 3 units in t h e later years.
ACKNOWLEDGMENTS
The authors thank Byron William Brown, Jr., for
advice on statistical aspects of the study and for helpful
comments on the manuscript. Jerry Halpern made the calculations depicted in Figure 2. J. T. Sibley assisted in
providing missing details about the Saskatoon databank and
made thoughtful suggestions on the manuscript. John Oehlert assisted by creating the merged data file using extracted
data from the 3 study centers. May Haga, Mary Ann Cathey,
and Melinda Tharan assisted in data collection in Saskatoon,
Wichita, and Denver, respectively.
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