Bone and Joint Research Unit and
1 Department of Psychological Medicine, Barts and The London, Queen Mary's School of Medicine and Dentistry,
2 National Sports Medicine Institute and
3 Barts and The London NHS Trust, London, UK
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Abstract |
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Methods. Ninety-three patients with systemic lupus erythematosus without active disease in any major organ were randomized, using a minimization protocol, to 12 weeks of graded exercise therapy, relaxation therapy or no intervention.
Results. Analysis by intention to treat showed that 16 of the 33 (49%) patients in the exercise group rated themselves as much or very much better compared with eight out of 29 (28%) in the relaxation group and five out of 32 (16%) in the control group (2=8.3, df=2, P=0.02). Fatigue improved significantly on one out of three measures after exercise therapy and there was a trend for fatigue to improve on all measures after exercise.
Conclusion. These findings support the use of appropriately prescribed graded aerobic exercise in the management of patients with fatigue and systemic lupus erythematosus.
KEY WORDS: Fatigue, Exercise, SLE, Randomized controlled trial.
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Introduction |
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In a randomized trial we compared the physiological, symptomatic and functional changes associated with a 12-week programme of either aerobic exercise therapy or relaxation therapy or no intervention.
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Patients and methods |
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Power calculation
In a previous study of exercise therapy and fibromyalgia, 50% of patients considered themselves moderately improved by the treatment compared with 10% of controls receiving flexibility training [10]. By assuming similar treatment responses with =0.05 and a power of 90%, we calculated that 30 subjects would be required for each group.
Methods
Symptomatic measures
Fatigue was measured with the Fatigue Severity Score (FSS) [14], the Chalder Fatigue Scale [15] and a visual analogue scale (VAS) [16]. Quality of sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI) [17], functional status was measured using the Medical Outcomes Study Short-Form Health Survey (SF-36) [18] and anxious and depressed moods were assessed using the Hospital Anxiety and Depression scale (HAD) [19]. Disease activity was measured using the Systemic Lupus Activity Measure (SLAM) [20] and disease damage was measured using the Systemic Lupus International Collaborating Clinics (SLICC)/ACR Damage Index [21]. A single rheumatologist performed all assessments of disease activity and damage.
Physiological assessments
The physiological assessments have been described in detail in a previous study [1] and included peak oxygen consumption (VO2peak), maximum ventilation, maximum heart rate and recovery heart rate measured during a walking test carried out on a motor-driven treadmill, and body mass index.
Treatments
All 93 patients were randomly allocated to the exercise programme, the relaxation programme or to no intervention, using a minimization protocol [22].
Exercise group
The patients were asked to exercise at home at least three times a week for between 30 and 50 min for a period of 12 weeks at a heart rate corresponding to 60% of peak oxygen consumption. The main exercise was walking but patients were encouraged to take other forms of exercise, such as cycling and swimming, and were seen every 2 weeks for a supervised exercise session.
Relaxation group
The patients were asked to listen to a 30-min relaxation audiotape a minimum of three times a week in a darkened, warm and quiet room and were seen every 2 weeks for a supervised relaxation session.
No intervention group
The patients were asked to continue with their normal daily activity pattern and specifically asked to avoid doing any extra physical activities. They were reviewed at follow-up but not seen at other times.
Outcome measures
The main outcome measure was the self-rated clinical global impression change score, which is a validated measure of overall change compared with study onset. It has seven possible scores, from very much worse (score 7) to very much better (score 1) [23]. Secondary outcome measures included assessments of symptoms, functional capacity and fitness, as described above.
Follow-up
After 12 weeks all patients were reassessed as at baseline. Three months after stopping supervised treatment, patients were reassessed with respect to symptoms and disease activity.
Statistical analysis
Statistical analysis used the SPSS 10.0 for Windows software package (SPSS, Chicago, IL, USA). All patients who underwent random allocation were analysed according to group assignment. The clinical global impression change score was analysed categorically; a score of 1 or 2 was considered clinically important. We compared the proportions of patients rating themselves clinically improved by intention-to-treat analysis by means of 2 analysis with Fisher's exact test for small numbers. One-way ANOVA (analysis of variance) with Bonferroni correction or the KruskalWallis test was used to compare means and medians of each variable in the three groups as appropriate. All P values were two-tailed. We completed follow-up assessments at 12 weeks on eight of the 11 patients who dropped out of treatment and included these data in the intention-to-treat analysis. Patients with missing data were counted as non-improvers for the purpose of the clinical global change score, and for all other secondary outcomes the last available data point was used.
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Results |
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Treatment results
Table 3 shows the main outcome of treatment. Sixteen of the 33 (49%) patients in the exercise group rated themselves as much or very much better compared with eight out of 29 (28%) in the relaxation group and five out of 32 (16%) in the control group (
2=8.3, df=2, P=0.02).
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At 12 weeks of treatment
After 12 weeks of treatment there was significant improvement in fatigue measured using the Chalder Fatigue Scale, but no significant differences between the groups for any of the other symptomatic measures (Table 1) or physiological measures (Table 2
). There was, however, a significant increase in exercise duration in the exercise group [exercise group 1.7 min (0.6), relaxation group 0.2 (0.4), control group -0.3 (0.4), P=0.01; Bonferroni correction, exercise vs control group P=0.009, exercise vs relaxation group P=0.08].
Dropouts from therapy
Six patients in the exercise group (one with mild disease flare, one with back pain, one with worse fatigue and three too busy) and four in the relaxation group (two too busy, one did not like audio tape and one did not want to participate after randomization) dropped out of treatment (did not attend a single supervised exercise class or return any diary sheets), and one person in the control group unexpectedly left the country. Fourteen patients (five in the relaxation group, five in the control group and four in the exercise group) did not attend for the 12-week physiological assessment. Six of these 14 patients had dropped out of treatment and eight had completed the study but did not wish to repeat the walking test to exhaustion.
Compliance
The median (interquartile range) number of supervised sessions attended by those completing therapy was 5 (45) in the exercise group and 4 (25) in the relaxation group. The median number of home exercise sessions was 35 (2540) and the median number home relaxation sessions was 33 (1236), with a median duration of 30 min for each session.
At 3 months of follow-up
Eighty-three of the original 93 patients were reassessed 3 months after stopping supervised treatment. There was a significant difference in the SF-36 vitality scale between the groups [exercise group, mean (S.E.M.) 51 (4), relaxation group 41 (4), control group 34 (4), one-way ANOVA P=0.015; Bonferroni correction, exercise vs control group P=0.012, others not significant) and the SF-36 role physical scale [exercise group, median (interquartile range) 75 (0100), relaxation group 0 (075), control group 25 (050), KruskalWallis P=0.024], but no other significant differences in symptomatic measures, disease activity or damage. Eight of the 33 patients in the exercise group continued to exercise regularly. There was a significant difference at 3 months of follow-up in the VAS fatigue score and Chalder Fatigue Scale of the eight patients who continued to exercise compared with the 25 patients who did not [mean (S.E.M.) VAS, exercise group 195 (23) vs no exercise group 270 (14), P=0.01; median (interquartile range) Chalder Fatigue Scale, exercise group 11 (517) vs no exercise group 17 (1226), P=0.05, FSS not significant].
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Discussion |
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It is interesting that the SF-36 vitality and role physical scales showed significant improvements after exercise therapy at the 3-month follow-up. However, the fact that this was not seen the end of the 12-week intervention period suggests this may not be a reliable finding and may simply reflect sample attrition.
Exercise duration increased by 18% after exercise therapy compared with a 3% reduction in the no intervention group, but there was no significant change in aerobic fitness. This change in exercise duration is likely to be due to improved exercise tolerance and is important because improved exercise capacity may reflect improvements in physical disability. However, this was not supported by any significant changes in self-perceived measures of physical function. There was no flare in disease activity with exercise and there were no serious adverse events.
Comparison with other published studies
The overall improvement after exercise therapy in this study is very similar to the size of effect seen in chronic fatigue syndrome [11]. Similarly, the improvement in fatigue demonstrated in this study after exercise therapy is similar to the improvements seen in other published trials of exercise in SLE. Robb-Nicholson et al. studied 23 patients with SLE and showed a significant change in fatigue after 8 weeks of exercise therapy using a VAS, but no significant difference using the Profile of Mood States fatigue subscale [24]. The size of the effect was very similar, with a mean improvement in fatigue after exercise therapy of 64 on a 400-point scale compared with a mean improvement in fatigue of 61 in this study. Daltroy et al. randomized 37 patients with rheumatoid arthritis and 34 patients with SLE to either stationary bicycling at home for 12 weeks or to no intervention, and showed a significant improvement in fatigue after exercise therapy using the Profile of Mood States fatigue subscale (P=0.03) [25]. However, these results are difficult to interpret because they represent the combined data from both SLE and RA patients. In both these studies there was no flare in disease activity after exercise, which is reassuring.
The fact that aerobic fitness did not change after exercise therapy is surprising. Robb-Nicholson et al. found a 19% improvement in VO2peak after exercise therapy, although this just failed to reach significance, and a 12% improvement in exercise duration [24]. Patients with chronic fatigue syndrome have also been shown to increase their VO2peak by 13% after 12 weeks of exercise therapy [11] and healthy sedentary normal subjects by between 5 and 10% [26]. The fact that the patients in this study did not significantly increase their aerobic fitness probably reflects the relatively easy exercise programme they were given (only 90 min of exercise per week at its maximum and only 60% of vo2max level of intensity). In addition, poor compliance with therapy may have been a factor.
Limitations of this study
The limitations of this study include the fact that patients with very active disease or serious organ involvement were excluded by design and that 31 eligible patients declined to participate, mostly citing a lack of spare time due to family or work commitments. This limits the generalizability of the results, particularly to those with more end-organ damage.
Summary
These findings support the use of appropriately prescribed graded aerobic exercise in the management of fatigue in patients with SLE. Exercise can be safely prescribed without exacerbating disease activity and leads to overall improvement when compared with relaxation therapy or no intervention. Greater improvement probably requires more intensive and/or frequent exercise, and sustained improvement probably requires continued exercise after the formal supervised programme is over.
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Acknowledgments |
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Notes |
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References |
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