7 Long-term effects of treating rheumatoid arthritis J O H A N N E S J. R A S K E R JOHN A. COSH
INTRODUCTION The clinical course of patients with rheumatoid arthritis (RA) is very varied. In a fortunate minority the disease remits, leaving little or no damage; by contrast, in the most badly affected patients the disease progresses relentlessly, bringing disability and complications that may threaten or end life itself. But the majority follows a course between these extremes, experiencing remissions and relapses, or continued mild disease activity over a long period of years with slowly progressive joint damage (Rasker and Cosh, 1989). This may carry serious implications for patients and their families, affecting working and earning capacity, eroding the quality of daily life and straining family relationships with potentially disastrous social and economic disadvantage (Meenan et al, 1981; McDuffie, 1985; Cornelissen et al, 1988). In the long term, treatment must be directed with an awareness not only of the disease process but also of its impact on all aspects of the patient's life. Continuity of care and periodic review are needed, in a clinic served by a co-operative team whose members include a nurse, physiotherapist and occupational therapist, availability of aids and splints with technical backup, orthopaedic surgery and, on the home front, general practitioner and practice nurse. The rheumatologist's role is one of periodic assessment and advice on overall management, with the help of other members of the team as necessary. The primary aim is to combat the inflammatory disease process, aiding functional recovery, and limiting structural damage as far as possible. Drugs are a major weapon for the rheumatologist. Since the introduction of gold as a second-line therapy some 60 years ago, other so-called diseasemodifying antirheumatic drugs (DMARDs) have been introduced. Some, such as antimalarials and penicillamine, have continued in use, while others (e.g. levamisole) have been dropped. Most such drugs have brought improvement over a period of 1-2 years, suggesting that they might also modify the long-term course of the disease, improving life expectancy, disability, quality of life and ability to work. However, long-term studies of Bailti~re's ClinicalRheumatology-Vol. 6, No. 1, February 1992 ISBN 0-7020-1635-7
141 Copyright 9 1992, by Bailli~re Tindall All rights of reproduction in any form reserved
142
J . J . R A S K E R A N D J. A . C O S H
the course of R A over 10-25 years reveal that the disease continues to cause excess mortality and morbidity despite the action of such DMARDs. It is difficult to evaluate the long-term effect of treatment on R A because there are no data on the course of the untreated disease. Several follow-up studies have been reported (Short and Bauer, 1948; Cobb et al, 1953; Duthie et al, 1964; Uddin et al, 1970; Monson and Hall, 1976; Allebeck, 1982; Vandenbroucke et al, 1984; Mutru et al, 1985; Scott et al, 1987; Ehrhardt et al, 1989), but comparison between them is difficult because of differences of method and patient selection. Such studies may be prospective (Vandenbroucke et al, 1984) or retrospective (Monson and Hall, 1976); they may be based on hospital inpatients (Cobb et al, 1953; Duthie et al, 1964) or outpatients (Jacoby et al, 1973), and early reports may well have included patients with arthritis due to Reiter's disease, viral infections or psoriatic arthritis. THE BATH STUDY
We base this review on our experiences with the Bath series of patients with RA, because this is the only long-term study in which all patients were treated and followed up from the beginning of the disease. From such a review of a large number of patients treated in a specialist rheumatology centre, a comprehensive view may be obtained of the long-term results of treatment. We shall consider the lessons learned, particularly from reviews of this series of patients between 15 and 25 years from the onset of RA. Patients and methods
The 100 patients formed a consecutive series of all patients with R A seen within a year of onset by J.A.C. Patients were accepted into the series if, by 1 year from onset, they met the American Rheumatology Association (ARA) criteria for definite or classical RA (Steinbrocker et al, 1949). The initial purpose was to study the disease in its earliest stages while details of its mode of onset were fresh in each patient's memory. They were 36 men and 64 women of ages ranging from 18 to 81 years (mean 50.6 years) and the mean duration of R A when they were first seen was 3.6 months (Jacoby et al, 1973; Rasker and Cosh, 1984). All were treated in the Royal National Hospital for Rheumatic Diseases, Bath, UK, and all survivors were reviewed at 3, 11, 15, 18, 20 and 25 years (Cosh and Rasker, 1982; Jacoby et al, 1973; Rasker and Cosh, 1984, 1987; Reilly et al, 1990). Information on each patient's condition was available for analysis on A R A grading (Ropes, 1959), functional capacity (Steinbrocker et al, 1949), joint score (Jacoby et al, 1973), presence of nodule and other clinical details; laboratory investigations included erythrocyte sedimentation rate (ESR) (Westergren), haemoglobin and Rose Waaler titre. Causes of death
By 25 years, 63 patients had died, 12 deaths were due directly to R A and its
L O N G - T E R M EFFECTS O F T R E A T I N G RA
143
systemic complications; nine deaths were due to other causes but with RA or its treatment as a contributory factor; and 42 deaths were from causes unrelated to RA. In none of the patients did D M A R D treatment cause death, but corticosteroid treatment may have contributed (Rasker and Cosh, 1981, 1987,1989; Reilly et al, 1990). Treatment
A detailed analysis of drug treatment was made at the time of the 15-year review (Rasker and Cosh, 1984).
Hospital admissions By that time 65 patients were still alive, of whom 50 had had a period of inpatient treatment; 20 were admitted once, but the remaining 30 had a total of 132 hospital admissions among them. At the time of the 3-year review, patients who had had inpatient treatment had a worse functional capacity and a worse disease category than the rest; this was no longer the case at the 11- and 15-year reviews (possibly explained by the fact that many patients out of the severe category had died in the meantime).
Drugs Virtually all patients had taken paracetamol and aspirin in various forms; 35 had started phenylbutazone and 30 indomethacin. After the 15-year review we felt that there was little to be gained from analysing the use of the many non-steroidal anti-inflammatory drugs (NSAIDs) then coming into use (Rasker and Cosh, 1984).
Second-line drugs Hydroxychloroquine was given to 55 of 65 patients, mostly 200 mg two or three times daily for 3-12 months, continuing longer if beneficial. No ocular complications were encountered in spite of regular checks by ophthalmologist. Myocrysin (sodium aurothiomalate) was given to 35 of 65 patients, 21 having a single course and the remainder between two and four courses. Initially, all courses were of 50 mg weekly up to a total of 1000 mg, but later often continuing with 50 mg monthly. Most patients reported benefit, but in 12 patients the drug was stopped because of skin rash, one with diarrhoea, another with proteinuria and in two because of lack of response. Penicillamine was given to eight patients in all (500-750 mg daily) and continued beyond 6 months in only four cases. Of the cytotoxic drugs, azathioprine was given to five patients and methotrexate to one patient who also had psoriasis.
Corticosteroids Corticosteroids were given to 29 of the surviving 65 patients at the time of the 15-year review, usually as prednisolone 2.5-7.5 mg daily. These patients
144
J.J.
RASKER A N D J. A. C O S H
were significantly worse than the rest regarding functional capacity ( P < 0.001) joint score, ESR, presence of nodules and high platelet count ( P < 0.05). They did not differ in A R A category, haemoglobin or Rose titre (Rasker and Cosh, 1984). Of the initial 100 patients, 49 were given corticosteroids; those patients who died from R A or its treatment had almost always received corticosteroids, indicating the more serious nature of their disease. No association was found between corticosteroid treatment and death from cardiovascular disease (Rasker and Cosh, 1981, 1987). Corticosteroid treatment correlated with subluxation in the cervical spine, radiological abnormalities in metacarpophalangeal and carpal joints, and mutilans deformities in hands (Rasker and Cosh, 1978) (see Radiology below).
Orthopaedic surgery During the first 15 years of disease, 29 of 65 survivors had undergone a total of 65 operations. The commonest at that time was knee synovectomy (17 times), and surgery of hands, wrists and feet. Most operations were performed from the eighth year onwards. The 11 operations done during the first 7 years included carpal tunnel release and repair of ruptured extensor pollicis tendon (Rasker and Cosh, 1984). After 25 years, operations in the 37 survivors were analysed (Reilly et al, 1990). Only three of the 11 patients then in functional class I had needed surgery, which was of a minor nature; patients in class II had a mean of three operations each, and those in class III and IV underwent a mean of five operations each, involving total hip and/or knee replacement. There can be no doubt that the functional capacity of many patients after 25 years in class II and III would have been worse without surgery (Reilly et al, 1990). Patterns of disease
The patterns of the course of the disease were divided into three categories: 1. 2. 3.
Remitting: initially active RA for up to 5 years, but with no sustained return of active disease thereafter. Chronic remitting and relapsing: periods of remission lasting 12 months or more, but with intermittent return to active disease. Chronic persistent: sustained disease activity with no remission lasting for as long as 12 months.
After 20 years, 16 of the 54 survivors are male (mean age 67 years) and 38 are female (mean age 63 years). The disease has been remitting in 12 cases, chronic remitting and relapsing in 12, and chronic persistent in 25; five had an atypical course (Table 1) (Rasker and Cosh, 1987). The remitting course was associated with good functional outcome. In these patients we saw a falling ESR, rising haemoglobin, static joint score and fall in rheumatoid factor titre, mostly converting to seronegative; only three of these patients required minor orthopaedic surgery (Reitly et al, 1990).
145
LONG-TERM EFFECTS OF TREATING RA Table 1. Pattern of disease over 20 years and functional grading. Functional capacity grade
Patients Pattern
No.
M
F
Seropositive
I and II
III and IV
Remitting Chronic relapsing Chronic persistent Atypical
12 12 25 5
5 3 4 4
7 9 21 1
2 5 17 1
9 8 9 4
3 4 16 1
Total
54
16
38
25
30
24
The patients with chronic remitting and relapsing and chronic persistent RA were much worse regarding functional capacity and joint damage, and required a mean of three orthopaedic operations. We cannot claim that this remitting pattern is the result of treatment, but probably have to see it as a spontaneous dying down of the disease process in some patients, marked by an improvement in the indices of inflammation and joint damage and a fall in rheumatoid factor titre.
Functional capacity After 20 years of disease, 55% of the survivors had still good function (Steinbrocker grade I or II) and 45% had poor function (grade III or IV) (Steinbrocker et al, 1949). A significant deterioration in functional capacity was seen in the reviews at 3, 11 and 15 years, affecting women more than men. Between 3 and 15 years only 28% of the patients remained in the same grade and the others deteriorated by one, two or even three grades (Table 2) (Rasker and Cosh, 1984). A slight improvement of the functional capacity was seen in the survivors between the 15- and 20-year follow-up studies, which may well be explained by the orthopaedic operations performed in these patients (Rasker and Cosh, 1987). An alternative explanation is that the deaths occurred mainly among the severely affected patients, leaving the better cases as survivors (Rasker and Cosh, 1981).
Table 2. Functional capacity in the 65 patients compared at 3 and 15 years (from Rasker and Cosh, 1984). At the 3-year review Grade
I
II
III
IV
No. of patients
43
19
2
1
Grade I
At the 15-year review
II III IV
9
23 25 8
9~0 0 0 17~6~0 0 14 9 ~2~ 0 3 4 0~1~18
146
J. J. RASKER AND J. A. COSH Table 3. Functional capacity as measured at last review in those patients who died (from Rasker and Cosh, 1989).
Functional capacity grade*
Review 3 years 11 years 15 years 18 years Total
I
II
III
IV
Total
7 4 1 0
2 3 1 1
5 4 1 1
3 7 5 1
17 18 8 3
12
7
11
16
46
* See Steinbrocker et al (1949),
At the 20-year review, we studied the functional capacity as noted at the last review before death (Table 3). It appeared that of the 46 who had died, 35% were already wheelchair-bound or bedridden at that time (grade IV) and 11 (24%) were limited to self-care and fit for little or none of the duties of usual occupation (grade III). The true state of these patients in the last few years before their deaths may well have been worse, as our assessments were made between 1 and 8 years before death and it may be expected that in many patients the functional capacity tended to deteriorate further (Rasker and Cosh, 1984). Our figures cannot be explained completely by a cause of death due to or related to RA; although most patients who died from RA or in whom disease or treatment contributed ended up in functional capacity III or IV, also in the unrelated group almost half of the patients ended in grade III or IV (Rasker and Cosh, 1989). These figures make clear that at least 59% of the patients with classical or definite RA will ultimately become severely dependent on others or completely confined to chair or bed. Thus, the prognosis of functional capacity in RA is much worse than mentioned in other series (Short and Bauer, 1948; Duthie et al, 1964; Scott et al, 1987). This may be explained by the fact that in all series only functional capacity of the survivors was measured and not the functional capacity during the last years before death. This same phenomenon can be shown in our own figures (Table 4). Table 4. Functional capacity as measured at 20 and 25 years in survivors and in those patients who had died, whose functional capacity was taken as that measured at the last review.
Survivors
Functional capacity grade I II III IV Values are percentages.
Dead
20 years
25 years
at last review
24 31 39 6
35 40 16 8
26 15 24 35
147
LONG-TERM EFFECTS OF TREATING RA
Functional capacity in relation to mortality One year after the onset of R A the functional capacity was already worse in those patients who subsequently died as a result of RA at the times of the 20and 25-year reviews when compared with those who survived (Table 5) (Rasker and Cosh, 1989). Table 5. Functional capacity after 1 year of disease of patients who died after 20 years and of survivors.
Function capacity grade at 1 year I II III and IV
Attributable/contributory
Unrelated
Survivors
13" 62 25
50 43 7
58 35 7
Values are percentages. Fisher exact test: * P < 0.005 versus survivors; P < 0.01 versus unrelated (two tailed).
ARA grading At the end of the first year all patients had by definition either 'definite' (n = 48) or 'classical' (n = 52) RA. The age at onset was nearly equal (49.9 and 51.3 years, respectively). At subsequent reviews some of the survivors had improved sufficiently to be recategorized as having probable or possible R A (at 11 years, 28%; at 15 years, 11%; at 20 years, 24%). The A R A category at 1 year proved to be a prognostic guide in the survivors, as those with definite R A were significantly better off regarding functional capacity, joint score, Ritchie index and more became seronegative (Rasker and Cosh, 1987). Also regarding death, the A R A category at 1 year proved a prognostic measure. The final figures for death were significantly different (P = 0.01) (Rasker and Cosh, 1981); this is made clear in Figure 1. Also, significantly more patients with classical R A at the end of the first year died from RA or its treatment than those with definite R A (P
INTRODUCTION The clinical course of patients with rheumatoid arthritis (RA) is very varied. In a fortunate minority the disease remits, leaving little or no damage; by contrast, in the most badly affected patients the disease progresses relentlessly, bringing disability and complications that may threaten or end life itself. But the majority follows a course between these extremes, experiencing remissions and relapses, or continued mild disease activity over a long period of years with slowly progressive joint damage (Rasker and Cosh, 1989). This may carry serious implications for patients and their families, affecting working and earning capacity, eroding the quality of daily life and straining family relationships with potentially disastrous social and economic disadvantage (Meenan et al, 1981; McDuffie, 1985; Cornelissen et al, 1988). In the long term, treatment must be directed with an awareness not only of the disease process but also of its impact on all aspects of the patient's life. Continuity of care and periodic review are needed, in a clinic served by a co-operative team whose members include a nurse, physiotherapist and occupational therapist, availability of aids and splints with technical backup, orthopaedic surgery and, on the home front, general practitioner and practice nurse. The rheumatologist's role is one of periodic assessment and advice on overall management, with the help of other members of the team as necessary. The primary aim is to combat the inflammatory disease process, aiding functional recovery, and limiting structural damage as far as possible. Drugs are a major weapon for the rheumatologist. Since the introduction of gold as a second-line therapy some 60 years ago, other so-called diseasemodifying antirheumatic drugs (DMARDs) have been introduced. Some, such as antimalarials and penicillamine, have continued in use, while others (e.g. levamisole) have been dropped. Most such drugs have brought improvement over a period of 1-2 years, suggesting that they might also modify the long-term course of the disease, improving life expectancy, disability, quality of life and ability to work. However, long-term studies of Bailti~re's ClinicalRheumatology-Vol. 6, No. 1, February 1992 ISBN 0-7020-1635-7
141 Copyright 9 1992, by Bailli~re Tindall All rights of reproduction in any form reserved
142
J . J . R A S K E R A N D J. A . C O S H
the course of R A over 10-25 years reveal that the disease continues to cause excess mortality and morbidity despite the action of such DMARDs. It is difficult to evaluate the long-term effect of treatment on R A because there are no data on the course of the untreated disease. Several follow-up studies have been reported (Short and Bauer, 1948; Cobb et al, 1953; Duthie et al, 1964; Uddin et al, 1970; Monson and Hall, 1976; Allebeck, 1982; Vandenbroucke et al, 1984; Mutru et al, 1985; Scott et al, 1987; Ehrhardt et al, 1989), but comparison between them is difficult because of differences of method and patient selection. Such studies may be prospective (Vandenbroucke et al, 1984) or retrospective (Monson and Hall, 1976); they may be based on hospital inpatients (Cobb et al, 1953; Duthie et al, 1964) or outpatients (Jacoby et al, 1973), and early reports may well have included patients with arthritis due to Reiter's disease, viral infections or psoriatic arthritis. THE BATH STUDY
We base this review on our experiences with the Bath series of patients with RA, because this is the only long-term study in which all patients were treated and followed up from the beginning of the disease. From such a review of a large number of patients treated in a specialist rheumatology centre, a comprehensive view may be obtained of the long-term results of treatment. We shall consider the lessons learned, particularly from reviews of this series of patients between 15 and 25 years from the onset of RA. Patients and methods
The 100 patients formed a consecutive series of all patients with R A seen within a year of onset by J.A.C. Patients were accepted into the series if, by 1 year from onset, they met the American Rheumatology Association (ARA) criteria for definite or classical RA (Steinbrocker et al, 1949). The initial purpose was to study the disease in its earliest stages while details of its mode of onset were fresh in each patient's memory. They were 36 men and 64 women of ages ranging from 18 to 81 years (mean 50.6 years) and the mean duration of R A when they were first seen was 3.6 months (Jacoby et al, 1973; Rasker and Cosh, 1984). All were treated in the Royal National Hospital for Rheumatic Diseases, Bath, UK, and all survivors were reviewed at 3, 11, 15, 18, 20 and 25 years (Cosh and Rasker, 1982; Jacoby et al, 1973; Rasker and Cosh, 1984, 1987; Reilly et al, 1990). Information on each patient's condition was available for analysis on A R A grading (Ropes, 1959), functional capacity (Steinbrocker et al, 1949), joint score (Jacoby et al, 1973), presence of nodule and other clinical details; laboratory investigations included erythrocyte sedimentation rate (ESR) (Westergren), haemoglobin and Rose Waaler titre. Causes of death
By 25 years, 63 patients had died, 12 deaths were due directly to R A and its
L O N G - T E R M EFFECTS O F T R E A T I N G RA
143
systemic complications; nine deaths were due to other causes but with RA or its treatment as a contributory factor; and 42 deaths were from causes unrelated to RA. In none of the patients did D M A R D treatment cause death, but corticosteroid treatment may have contributed (Rasker and Cosh, 1981, 1987,1989; Reilly et al, 1990). Treatment
A detailed analysis of drug treatment was made at the time of the 15-year review (Rasker and Cosh, 1984).
Hospital admissions By that time 65 patients were still alive, of whom 50 had had a period of inpatient treatment; 20 were admitted once, but the remaining 30 had a total of 132 hospital admissions among them. At the time of the 3-year review, patients who had had inpatient treatment had a worse functional capacity and a worse disease category than the rest; this was no longer the case at the 11- and 15-year reviews (possibly explained by the fact that many patients out of the severe category had died in the meantime).
Drugs Virtually all patients had taken paracetamol and aspirin in various forms; 35 had started phenylbutazone and 30 indomethacin. After the 15-year review we felt that there was little to be gained from analysing the use of the many non-steroidal anti-inflammatory drugs (NSAIDs) then coming into use (Rasker and Cosh, 1984).
Second-line drugs Hydroxychloroquine was given to 55 of 65 patients, mostly 200 mg two or three times daily for 3-12 months, continuing longer if beneficial. No ocular complications were encountered in spite of regular checks by ophthalmologist. Myocrysin (sodium aurothiomalate) was given to 35 of 65 patients, 21 having a single course and the remainder between two and four courses. Initially, all courses were of 50 mg weekly up to a total of 1000 mg, but later often continuing with 50 mg monthly. Most patients reported benefit, but in 12 patients the drug was stopped because of skin rash, one with diarrhoea, another with proteinuria and in two because of lack of response. Penicillamine was given to eight patients in all (500-750 mg daily) and continued beyond 6 months in only four cases. Of the cytotoxic drugs, azathioprine was given to five patients and methotrexate to one patient who also had psoriasis.
Corticosteroids Corticosteroids were given to 29 of the surviving 65 patients at the time of the 15-year review, usually as prednisolone 2.5-7.5 mg daily. These patients
144
J.J.
RASKER A N D J. A. C O S H
were significantly worse than the rest regarding functional capacity ( P < 0.001) joint score, ESR, presence of nodules and high platelet count ( P < 0.05). They did not differ in A R A category, haemoglobin or Rose titre (Rasker and Cosh, 1984). Of the initial 100 patients, 49 were given corticosteroids; those patients who died from R A or its treatment had almost always received corticosteroids, indicating the more serious nature of their disease. No association was found between corticosteroid treatment and death from cardiovascular disease (Rasker and Cosh, 1981, 1987). Corticosteroid treatment correlated with subluxation in the cervical spine, radiological abnormalities in metacarpophalangeal and carpal joints, and mutilans deformities in hands (Rasker and Cosh, 1978) (see Radiology below).
Orthopaedic surgery During the first 15 years of disease, 29 of 65 survivors had undergone a total of 65 operations. The commonest at that time was knee synovectomy (17 times), and surgery of hands, wrists and feet. Most operations were performed from the eighth year onwards. The 11 operations done during the first 7 years included carpal tunnel release and repair of ruptured extensor pollicis tendon (Rasker and Cosh, 1984). After 25 years, operations in the 37 survivors were analysed (Reilly et al, 1990). Only three of the 11 patients then in functional class I had needed surgery, which was of a minor nature; patients in class II had a mean of three operations each, and those in class III and IV underwent a mean of five operations each, involving total hip and/or knee replacement. There can be no doubt that the functional capacity of many patients after 25 years in class II and III would have been worse without surgery (Reilly et al, 1990). Patterns of disease
The patterns of the course of the disease were divided into three categories: 1. 2. 3.
Remitting: initially active RA for up to 5 years, but with no sustained return of active disease thereafter. Chronic remitting and relapsing: periods of remission lasting 12 months or more, but with intermittent return to active disease. Chronic persistent: sustained disease activity with no remission lasting for as long as 12 months.
After 20 years, 16 of the 54 survivors are male (mean age 67 years) and 38 are female (mean age 63 years). The disease has been remitting in 12 cases, chronic remitting and relapsing in 12, and chronic persistent in 25; five had an atypical course (Table 1) (Rasker and Cosh, 1987). The remitting course was associated with good functional outcome. In these patients we saw a falling ESR, rising haemoglobin, static joint score and fall in rheumatoid factor titre, mostly converting to seronegative; only three of these patients required minor orthopaedic surgery (Reitly et al, 1990).
145
LONG-TERM EFFECTS OF TREATING RA Table 1. Pattern of disease over 20 years and functional grading. Functional capacity grade
Patients Pattern
No.
M
F
Seropositive
I and II
III and IV
Remitting Chronic relapsing Chronic persistent Atypical
12 12 25 5
5 3 4 4
7 9 21 1
2 5 17 1
9 8 9 4
3 4 16 1
Total
54
16
38
25
30
24
The patients with chronic remitting and relapsing and chronic persistent RA were much worse regarding functional capacity and joint damage, and required a mean of three orthopaedic operations. We cannot claim that this remitting pattern is the result of treatment, but probably have to see it as a spontaneous dying down of the disease process in some patients, marked by an improvement in the indices of inflammation and joint damage and a fall in rheumatoid factor titre.
Functional capacity After 20 years of disease, 55% of the survivors had still good function (Steinbrocker grade I or II) and 45% had poor function (grade III or IV) (Steinbrocker et al, 1949). A significant deterioration in functional capacity was seen in the reviews at 3, 11 and 15 years, affecting women more than men. Between 3 and 15 years only 28% of the patients remained in the same grade and the others deteriorated by one, two or even three grades (Table 2) (Rasker and Cosh, 1984). A slight improvement of the functional capacity was seen in the survivors between the 15- and 20-year follow-up studies, which may well be explained by the orthopaedic operations performed in these patients (Rasker and Cosh, 1987). An alternative explanation is that the deaths occurred mainly among the severely affected patients, leaving the better cases as survivors (Rasker and Cosh, 1981).
Table 2. Functional capacity in the 65 patients compared at 3 and 15 years (from Rasker and Cosh, 1984). At the 3-year review Grade
I
II
III
IV
No. of patients
43
19
2
1
Grade I
At the 15-year review
II III IV
9
23 25 8
9~0 0 0 17~6~0 0 14 9 ~2~ 0 3 4 0~1~18
146
J. J. RASKER AND J. A. COSH Table 3. Functional capacity as measured at last review in those patients who died (from Rasker and Cosh, 1989).
Functional capacity grade*
Review 3 years 11 years 15 years 18 years Total
I
II
III
IV
Total
7 4 1 0
2 3 1 1
5 4 1 1
3 7 5 1
17 18 8 3
12
7
11
16
46
* See Steinbrocker et al (1949),
At the 20-year review, we studied the functional capacity as noted at the last review before death (Table 3). It appeared that of the 46 who had died, 35% were already wheelchair-bound or bedridden at that time (grade IV) and 11 (24%) were limited to self-care and fit for little or none of the duties of usual occupation (grade III). The true state of these patients in the last few years before their deaths may well have been worse, as our assessments were made between 1 and 8 years before death and it may be expected that in many patients the functional capacity tended to deteriorate further (Rasker and Cosh, 1984). Our figures cannot be explained completely by a cause of death due to or related to RA; although most patients who died from RA or in whom disease or treatment contributed ended up in functional capacity III or IV, also in the unrelated group almost half of the patients ended in grade III or IV (Rasker and Cosh, 1989). These figures make clear that at least 59% of the patients with classical or definite RA will ultimately become severely dependent on others or completely confined to chair or bed. Thus, the prognosis of functional capacity in RA is much worse than mentioned in other series (Short and Bauer, 1948; Duthie et al, 1964; Scott et al, 1987). This may be explained by the fact that in all series only functional capacity of the survivors was measured and not the functional capacity during the last years before death. This same phenomenon can be shown in our own figures (Table 4). Table 4. Functional capacity as measured at 20 and 25 years in survivors and in those patients who had died, whose functional capacity was taken as that measured at the last review.
Survivors
Functional capacity grade I II III IV Values are percentages.
Dead
20 years
25 years
at last review
24 31 39 6
35 40 16 8
26 15 24 35
147
LONG-TERM EFFECTS OF TREATING RA
Functional capacity in relation to mortality One year after the onset of R A the functional capacity was already worse in those patients who subsequently died as a result of RA at the times of the 20and 25-year reviews when compared with those who survived (Table 5) (Rasker and Cosh, 1989). Table 5. Functional capacity after 1 year of disease of patients who died after 20 years and of survivors.
Function capacity grade at 1 year I II III and IV
Attributable/contributory
Unrelated
Survivors
13" 62 25
50 43 7
58 35 7
Values are percentages. Fisher exact test: * P < 0.005 versus survivors; P < 0.01 versus unrelated (two tailed).
ARA grading At the end of the first year all patients had by definition either 'definite' (n = 48) or 'classical' (n = 52) RA. The age at onset was nearly equal (49.9 and 51.3 years, respectively). At subsequent reviews some of the survivors had improved sufficiently to be recategorized as having probable or possible R A (at 11 years, 28%; at 15 years, 11%; at 20 years, 24%). The A R A category at 1 year proved to be a prognostic guide in the survivors, as those with definite R A were significantly better off regarding functional capacity, joint score, Ritchie index and more became seronegative (Rasker and Cosh, 1987). Also regarding death, the A R A category at 1 year proved a prognostic measure. The final figures for death were significantly different (P = 0.01) (Rasker and Cosh, 1981); this is made clear in Figure 1. Also, significantly more patients with classical R A at the end of the first year died from RA or its treatment than those with definite R A (P
