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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgments
  9. REFERENCES

Objective

To determine the effects of a 12-week endurance exercise program on health, disability, VO2 max, and disease activity in a multicenter randomized controlled trial in patients with established polymyositis (PM) and dermatomyositis (DM), and to evaluate health and disability in a 1-year open extension study.

Methods

Patients were randomized into a 12-week endurance exercise program group (EG; n = 11) or a control group (CG; n = 10). Assessments of health (Short Form 36 [SF-36]), muscle performance (5 voluntary repetition maximum [5 VRM]), activities of daily living (ADL), patient preference (McMaster Toronto Arthritis Patient Preference Disability Questionnaire), VO2 max, and disease activity (International Myositis Assessment and Clinical Studies criteria of improvement of the 6-item core set) were performed at 0 and 12 weeks. Disability assessments were performed again at 52 weeks in an open extension period. All assessments were performed by blinded observers.

Results

The EG improved compared to the CG in SF-36 physical function and vitality (P = 0.010 and P = 0.046, respectively), ADL score (P = 0.035), 5 VRM (P = 0.026), and VO2 max (P = 0.010). More patients in the EG (7 of 11) were responders with reduced disease activity compared to none in the CG (P = 0.002). Correlations between VO2 max and SF-36 physical function were 0.90 and 0.91 at 0 and 12 weeks, respectively (P < 0.05). The EG improvement in 5 VRM was sustained up to 52 weeks compared to baseline (5.7 kg; P < 0.001), but not in ADL score or SF-36.

Conclusions

Endurance exercise improves health and may reduce disease activity in patients with established PM/DM. This potentially could be mediated through improved aerobic fitness. The results also indicate sustained muscle strength up to 1 year after a supervised program.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgments
  9. REFERENCES

Polymyositis (PM) and dermatomyositis (DM) are characterized by low muscle function as the major clinical symptom ([1, 2]). Despite treatment with high doses of glucocorticoids and immunosuppressive agents, the majority of patients develop sustained disability and reduced health compared to the general population ([3-8]). VO2 max is an independent indicator of health ([9]). Low VO2 max was found in PM/DM patients compared to healthy controls ([10]). This may contribute to disability and reduced health in these patients.

Although a physically active lifestyle is fundamental to maintain health, patients with PM and DM previously were discouraged from exercise. However, recent exercise studies in established PM/DM reveal benefits without increased inflammatory markers ([11, 12]). Exercise may even reduce disease activity in inflammatory rheumatic conditions by lowering levels of systemic inflammation ([13, 14]). Lower disease activity was also observed after 7 weeks of intensive resistance training in patients with PM/DM ([15]). The clinical effect was accompanied by a reduction in expression of proinflammatory genes in muscle tissue ([16]).

One randomized controlled trial (RCT) of exercise was published on patients with PM/DM ([17]). This 6-week RCT resulted in improved VO2 max, muscle strength, and activities of daily living (ADL). Eight patients from the RCT continued to exercise for 6 months, resulting in further clinical improvement without an increase in serum creatine phosphokinase (CPK), suggesting safety and beneficial effects of long-term endurance training ([18]). Information on other aspects of long-term effects of exercise in patients with PM/DM is lacking. In addition, the effects of exercise on individual disease-related disabilities, identified for importance to improve, using a patient preference outcome measure have never been investigated in these patients.

We hypothesized that an endurance exercise intervention would benefit patients with established PM/DM compared to a noninterventional control group (CG) regarding health, disability, and disease activity. We also predicted maintained long-term effects of the endurance exercise program up to 1 year.

The objective of this multicenter RCT study was to determine whether a 12-week endurance exercise program could improve health, patient preference, ADL, muscle performance, and VO2 max and reduce disease activity, as well as to evaluate correlations between VO2 max and health. Furthermore, we aimed to evaluate muscle performance, patient preference, ADL, and health in a 1-year open extension study.

Box 1. Significance & Innovations

  • In this multicenter randomized controlled trial study, we demonstrated that 12 weeks of endurance exercise improves health, muscle performance, and VO2 max, and may reduce disease activity in polymyositis/dermatomyositis patients with established disease.
  • Improved health was strongly related to increased VO2 max.
  • The exercise group kept their improved muscle performance in a 1-year open extension followup period. On the contrary, other disability assessments returned to baseline values, indicating a need for regular physical exercise support to maintain improved health.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgments
  9. REFERENCES

Study design

The controlled part of the study was a multicenter RCT evaluating the effects of a supervised 12-week endurance exercise program compared to a noninterventional CG with a 52-week open extension followup period. Patients were recruited at 3 centers in Sweden: Karolinska University Hospital, Sahlgrenska University Hospital, and Uppsala University Hospital.

The study was approved by the local ethics review boards at Karolinska University Hospital, Sahlgrenska University Hospital, and Uppsala University Hospital. All patients signed informed consent before entering the study.

Patients

Patients with established PM/DM were recruited from 2007–2011. Inclusion criteria were 1) a diagnosis of definite or probable PM or DM ([19, 20]), 2) age >18 years, 3) duration since diagnosis >6 months, 4) exercising once a week or less, and 5) receiving stable medication for at least 1 month. Exclusion criteria were 1) severe heart or lung conditions, 2) severe osteoporosis, and 3) not being able to exercise.

Using a randomization list, patients (Table 1 and Figure 1) were randomized by an independent nurse into an exercise group (EG; n = 12) or a CG (n = 11). The physical therapist responsible for exercise coaching at each center was then contacted and informed about group allocation by the nurse. According to the ethical permit, patients in the CG were invited to participate in the exercise program after the 12-week intervention period. Two patients in the CG accepted this invitation and started to exercise according to the endurance exercise program after week 12. They were excluded in the 52-week analysis in the open extension part of the study.

Table 1. Demographic baseline data for the exercise group (n = 11) and the control group (n = 10), including recommended myositis core set measures for disease activity and damage*
 Exercise group (n = 11)aControl group (n = 10)a
  1. Values are the median (interquartile range) unless indicated otherwise. PM/DM = polymyositis/dermatomyositis; BMI = body mass index; DMARD = disease-modifying antirheumatic drug; GCs = glucocorticoids; MMT-8 = manual muscle strength testing in 8 muscle groups; HAQ = Health Assessment Questionnaire; CPK = creatine phosphokinase; VAS = visual analog scale; MITAX = Myositis Intent-to-Treat Activity Index.

  2. a

    No statistical differences between the exercise group and the control group in any of the variables using the Mann-Whitney U test (P < 0.05).

  3. b

    Normal weight = 18.5–24.9 kg/m2, overweight = 25.0–29.9 kg/m2, and obesity = ≥30.0 kg/m2.

  4. c

    N = 1 missing.

  5. d

    Normal values <2.5 μkat/liter in women and <3.0 μkat/liter in men.

  6. e

    N = 2 missing.

Sex, female/male10/16/4
Diagnosis, PM/DM5/64/6
Age, years62 (16)60 (15)
BMI, kg/m2b24.9 (2.1)26.9 (5.7)
Nonsmoker/smoker, no.11/09/1
Duration since diagnosis, years8 (8)8 (6)
DMARD treatment, no.  
GCs66
Methotrexate32
Azathioprine42
Rituximab02
Mycophenolate mofetil10
Cyclosporin A01
Daily GC dose, mg1.25 (5)2.50 (5)
MMT-8 (range 0–80)75 (9)75 (11)
HAQ (range 0.00–3.00)0.50 (0.37)c0.44 (0.25)
Serum CPK, μkat/literd1.7 (2.9)c1.7 (1.5)e
Physician's global disease activity (0–100 VAS)4 (10)c1 (10)c
Patient's global disease activity (0–100 VAS)22 (35)c42 (43)
MITAX (range 0.00–1.00)0.11 (0.11)0.13 (0.08)c
Global damage (0–100 VAS)28 (47)c18 (30)c
image

Figure 1. Flow diagram for patients according to the Consolidated Standards of Reporting Trials randomized controlled trials of nonpharmacologic treatment ([50]) and through the 1-year open extension part of the study. 1 = 1 dropout from the EG due to abdominal surgery and 1 for unknown reasons; 2 = 1 dropout in the CG for unknown reasons; 3 = 2 patients in the CG were excluded because of protocol reasons (started to exercise).

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Twelve-week endurance exercise program

The EG performed a 1-hour exercise program 3 times a week for 12 weeks consisting of cycling at 70% of VO2 max, aiming for 30 minutes. This was followed by 20 minutes of muscular endurance exercise of the knee extensors at ∼30–40% of 1 voluntary repetition maximum (1 VRM). During the first weeks, the exercise intensity was gradually increased from 50% up to 70% of the patients' individual VO2 max. The EG exercised twice a week at the physical therapy departments at each of the 3 centers, and once a week with the same program at home using an exercise bike and weight cuffs provided by the project. The CG was instructed not to change their exercise or physical activity level. All patients kept exercise diaries and the EG was supervised by the same physical therapist at each respective center. The exercise diaries were collected and all exercise equipment was returned at 12 weeks, and no further supervision or instructions regarding physical exercise were given to either the EG or the CG.

Assessments to test the hypothesis

Assessments of health, patient preference, limitation in ADL, muscle performance, and VO2 max were performed by a physical therapist at each respective center, blinded to the type of intervention (i.e., exercise or control) before and after the 12-week intervention and after 52 weeks. Assessment of disease activity was performed at the study start and after 12 weeks by the same rheumatologist at each respective center, blinded to the type of intervention.

Health

For assessment of health, we used the Short Form 36 (SF-36) comprising 8 domains (physical function, role physical, bodily pain, general health, vitality, social function, role emotional, and mental health). Each domain is scored from 0–100, where 100 = optimal health ([21]).

Patient preference

The McMaster Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR), a valid semistructured interview, was used to assess patient preference ([22]). The interviewer asked the patient to identify disabilities related to their PM/DM. Thereafter, the patient ranked the identified disabilities according to importance for improvement (patient preference) and the 5 highest ranked disabilities were recorded. The score varies between 19 and 39, where 39 = no disability ([22, 23]).

Limitations in ADL

The Myositis Activities Profile (MAP) is a valid disease-specific questionnaire assessing limitations in ADL ([24]). It consists of 31 items divided into 4 subscales (movement, moving around, personal care, and household) and 4 single items (social, overexertion, work, and leisure time activities) each scored from 1–7, where 1 = no difficulty and 7 = impossible ([24]).

Muscle performance

Five VRM measures of muscle strength, e.g., the maximum load the patient can lift in a full range of motion in 5 repetitions, were assessed in the knee extensors in a standardized sitting position from 90° of knee flexion to full knee extension in the left and right legs.

VO2 max

A VO2 max test was performed on an ergometer bicycle starting at 30–40W, and the required power output was increased by 10W every minute. VO2 max was determined by incremental cycling to exhaustion. Pulmonary minute ventilation and gas exchange (O2 uptake and CO2 output, respectively) were measured breath by breath (V max 229TM, SensorMedics). VO2 max was defined as the highest O2 uptake rate measured during the test, expressed as liters/minute−1, and the power performed (in W) at the time of VO2 max was recorded. To ensure that cycling was performed to exhaustion and therefore a measure of reliable VO2 max, we measured the respiratory exchange ratio, defined as the ratio between the exhaled CO2 and the inhaled O2. At the end of the test, patients rated self-reported peripheral and central exertion on the Borg rating of perceived exertion scale (range 6–20) ([25]). Electrocardiography was used continuously during the test.

Disease activity and damage

Assessment of disease activity was performed using the core set measures developed by the International Myositis Assessment and Clinical Studies (IMACS) group ([26]), including patient's and physician's global disease activity on a visual analog scale (VAS; range 0–100), manual muscle strength testing in 8 groups (MMT-8; range 0–80), Health Assessment Questionnaire (ADL, range 0–3), laboratory assessment of serum CPK (reference values <2.5 μkat/liter in women and <3.0 μkat/liter in men), and assessment of extraskeletal muscle disease activity in 6 organ systems using the Myositis Intent-to-Treat Activity Index and global extraskeletal muscle activity (measured on 0–100 VAS). Erythrocyte sedimentation rate (reference value <20 mm/hour), C-reactive protein level (reference value <3 mg/liter), and CPK were used for assessment of disease activity and to elucidate a flare in the open extension part of the study. Disease damage was measured at baseline by the global damage tool assessing severity of damage in 11 organ systems on a 0–100 VAS ([26, 27]).

Statistical analyses

Descriptive baseline data are shown as the median and interquartile range (Table 1). All data were analyzed with a mixed model using commercially available statistical software (Statsoft). Changes in SF-36, MACTAR, MAP, 5 VRM, MMT-8, VO2 max, physician's global disease activity, and global extraskeletal muscle activity during different intervals of time were analyzed using a mixed linear model involving time (0 and 12 weeks or 0, 12, and 52 weeks) as the within-subjects variable and group (EG and CG) as the between-subjects variable and the group × time interaction. Estimates from the mixed model are shown as the mean and 95% confidence interval (95% CI). Mixed models differ from conventional fixed-effects models in that they allow the variances and covariances in the data to be modeled. This leads to more appropriate fixed-effects estimates and SEs. Problems caused by imbalance when fitting fixed-effects models (subjects with missing data are excluded from the analysis) do not arise in mixed models, provided that missing data can be assumed missing at random ([28]). P values less than 0.05 were considered statistically significant. The alpha level was not adjusted for multiple comparisons because the different time points are not independent and adjustments could lead to an increase of false-negative findings.

For analysis of correlation between health (SF-36 physical function) and VO2 max (liters/minute and W), we used Pearson's correlation coefficient (r), where 0–0.25 = very little or little correlation, 0.26–0.49 = low correlation, 0.50–0.69 = moderate correlation, 0.70–0.89 = high correlation, and ≥0.90 = very high correlation ([29]). We used Statistica, version 10.0 (StatSoft), and SAS, system 9.1, statistical software.

A responder in muscle performance and VO2 max was defined as improving by ≥20% in 5 VRM or by ≥10% in VO2 max compared to baseline ([30]). To define reduced disease activity, the proposed definition by the IMACS group was used ([31]). To be a responder, a patient should improve by ≥20% in ≥3 of 6 IMACS core measures with no more than 2 worsened by ≥25%, which could not include MMT-8, since muscle weakness is the main symptom in PM/DM. Fisher's exact test was used to investigate the difference between the EG and the CG as to the frequencies of responders and nonresponders in disease activity, VO2 max, and 5 VRM. P values less than 0.05 were considered statistically significant. Data were analyzed and shown with sensitivity, specificity, and positive and negative likelihood ratios in relation to response in VO2 max versus in disease activity (MedCalc for Windows, version 12.5). Values are shown with 95% CIs.

A power analysis based on mean values of improvement and SEMs from a previous open exercise study in PM/DM ([15]) indicated a sample size of 15 patients in each group, giving 80% power to detect a significant difference in the intended primary outcome, the Functional Index 2 (FI-2). Because PM and DM are rare conditions, the research group decided at the study onset to perform an interim analysis in case patient recruitment did not proceed as quickly as projected. VO2 max was determined to be more sensitive to change than the FI-2 according to the type of exercise performed, and thereby was selected instead as the primary outcome and used for the interim analysis. After 4 years, an interim power analysis showed 86% power in the group × time interaction and a significant difference in VO2 max (and indicated a sample size of 9 patients in each group, giving 80% power to detect a significant difference in the primary outcome, VO2 max), and thereby patient recruitment was stopped.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgments
  9. REFERENCES

Effect of a 12-week endurance exercise program: controlled part

Twenty-three PM and DM patients (n = 12 in the EG and n = 11 in the CG) were included in the 12-week endurance exercise program. All patients were in a stable disease phase with no to high damage and with unchanged medication for at least 1 month before inclusion in the study, as well as during the 12-week intervention. One patient in the EG was not able to perform the exercise program and was excluded from the analysis (n = 11), while the remaining patients tolerated the exercise program well without adverse events. One patient in the CG participated in another exercise program and was excluded from the analysis (n = 10). Demographic data on the group level are shown in Table 1 and on the individual level are shown in Table 2.

Table 2. Results of VO2 max and muscle performance in the controlled part of the study: 12 weeks of endurance exercise in 11 patients (EG) and of nonexercise in 10 patients (CG)*
PatientGroupSexGlobal damage (0–100 VAS)Diagnosis duration, yearsVO2 max, liters/minVO2 max, W5 VRM, kg
Baseline12-wk followupBaseline12-wk followupBaseline12-wk followup
  1. Data were analyzed by criteria for clinical improvement in VO2 max and muscle performance ([30]). EG = exercise group; CG = control group; VAS = visual analog scale; 5 VRM = 5 voluntary repetition maximum in right knee extension; NA = not assessed.

  2. a

    Clinical improvement in disease activity according to the International Myositis Assessment and Clinical Studies criteria for patients with polymyositis/dermatomyositis ([31]).

  3. b

    Improved muscle performance (5 VRM) compared to baseline by ≥20% or VO2 max compared to baseline by ≥10%.

AaEGF2071.792.00b130150b2432b
BaEGF1191.611.84b120140b1517
CaEGM62112.202.47b170190b2123
DEGF60260.470.56b505012b
EaEGF5880.921.06b7080b913b
FaEGF931.441.53100120b1012b
GEGFNA131.010.91403011
HaEGF3281.601.80b113128b913b
IEGF24101.442.06b100120b310b
JEGF711.811.60130150b413b
KaEGF3711.301.68b100120b810b
LCGF1041.431.31110902324
MCGM082.112.071501403428
NCGF1881.511.291001002426
OCGM40283.33NA230NA1721b
PCGF1870.990.9890801112
QCGM4921.751.471201202022
RCGMNA31.451.63b96106b814b
SCGF471.44NA104NA55
TCGF25331.651.541301201817
UCGF41101.211.19908089
Improved health and correlation between VO2 max and health

The EG improved in the domains physical function and vitality compared to the CG (Table 3). Consistently, the EG improved in the domains physical function, general health, vitality, and mental health, while the CG remained unchanged (Table 3). Correlations between health (SF-36 domain physical function) and VO2 max (assessed in liters/minute and W) in the EG were 0.90 and 0.91 at baseline (P < 0.05), respectively, and were 0.91 and 0.97 at 12 weeks (P < 0.05), respectively.

Table 3. Changes in health, disease activity, muscle performance, patient preference, and activities in daily living in the 12-week controlled part of the study from baseline to 12-week followup for the EG and the CG*
Δ in variable (12-week followup vs. baseline)EG (n = 11)CG (n = 10)Group × time interaction, P
Estimate, mean (95% CI)PEstimate, mean (95% CI)P
  1. EG = exercise group; CG = control group; 95% CI = 95% confidence interval; SF-36 = Short Form 36; VAS = visual analog scale; MMT-8 = manual muscle strength testing in 8 muscle groups; 5 VRM = 5 voluntary repetition maximum in knee extensors; MACTAR = McMaster Toronto Arthritis Patient Preference Disability Questionnaire; MAP = Myositis Activities Profile.

  2. a

    Domains of the SF-36 and the MAP with nonsignificant changes are not reported.

  3. b

    Significant at P < 0.05.

SF-36 (scale 0–100)a     
Physical function8.9 (2.7, 15.2)0.001b−0.2 (−13.4, 12.9)0.7000.010b
General health15.5 (6.6, 24.3)0.002b6.0 (−3.7, 15.7)0.2090.148
Vitality11.8 (2.7, 21.0)0.007b−0.5 (−10.5, 9.6)0.8990.046b
Mental health8.1 (0.7, 15.5)0.034b3.1 (−5.1, 11.3)0.4390.355
Physician's global disease activity (0–100 VAS)−4 (−7, −1)0.017b−1 (−2, 1)0.3240.038b
Extramuscular disease activity (0–100 VAS)−2 (−4, −0)0.020b0 (−2, 2)0.8620.075
MMT-8 (range 0–80)4 (1, 7)0.015b3 (−3, 9)0.2940.735
VO2 max, liters/minute0.17 (0.05, 0.30)0.009b−0.09 (−0.23, 0.06)0.2270.010b
VO2 max, W14 (7, 21)< 0.001b−4 (−12, 3)0.2380.002b
5 VRM right, kg3.8 (2.0, 5.5)< 0.001b1.3 (−0.5, 3.1)0.1520.056
5 VRM left, kg3.8 (1.6, 5.9)0.002b1.1 (−2.1, 2.4)0.8910.026b
MACTAR (range 19–39)4 (2, 7)0.003b2 (−1, 5)0.1780.197
MAP (scale 1–7)a     
Moving around−0.3 (−0.7, 0.2)0.3260.7 (−0.1, 1.4)0.0640.035b
Household−0.1 (−0.5, 0.3)0.7120.6 (0.2, 1.1)0.029b0.064
Social−0.5 (−0.9, 0.0)0.020b0.0 (−0.4, 0.4)1.0000.097
Leisure activity−1.2 (−1.8, −0.6)0.011b−0.2 (−1.3, 0.9)0.7580.200
Improved muscle performance, VO2 max, and reduced disease activity

Eight patients in the EG were responders with improved 5 VRM, while 2 patients in the CG were responders (P = 0.023) (Table 2). These 8 patients and 2 additional patients in the EG were also responders in VO2 max compared to 1 patient in the CG (P = 0.002) (Table 3). Seven of 11 patients in the EG were responders with reduced disease activity (Table 4), whereas no patients in the CG were responders in disease activity (data not shown) (P = 0.002). All responders with reduced disease activity in the EG were also responders in VO2 max. Conversely, only 2 patients in the CG were responders with improved 5 VRM and 1 in VO2 max (Table 2). The sensitivity that a responder in VO2 max was also a responder in disease activity was 70% (95% CI 35%, 93%) and the specificity was 100% (95% CI 71%, 100%), with a negative likelihood ratio of 0.30 (95% CI 0.12, 0.77). A positive likelihood ratio was not possible to calculate. The CG patient who was a responder both in 5 VRM and VO2 max did not return the exercise diary; therefore, the exercise level could not be determined.

Table 4. Results of disease activity assessments in the controlled part of the study: 12 weeks of endurance exercise in 11 patients (exercise group)*
PatientPatient's global disease activity (0–100 VAS)Physician's global disease activity (0–100 VAS)MMT-8 (range 0–80)HAQ (range 0.00–3.00)CPK, μkat/literaMITAX (range 0.00–1.00)
Baseline12-wk followupBaseline12-wk followupBaseline12-wk followupBaseline12-wk followupBaseline12-wk followupBaseline12-wk followup
  1. Data were analyzed by criteria for minimum clinical improvement in disease activity according to the International Myositis Assessment and Clinical Studies criteria for patients with polymyositis/dermatomyositis ([31]). VAS = visual analog scale; MMT-8 = manual muscle strength testing in 8 muscle groups; HAQ = Health Assessment Questionnaire; CPK = creatine phosphokinase; MITAX = Myositis Intent-to-Treat Activity Index; NA = not assessed.

  2. a

    Normal values <2.5 μkat/liter in women and <3.0 μkat/liter in men.

  3. b

    Clinical improvement in disease activity compared to baseline by ≥20% in ≥3 measures with no more than 2 worsened by ≥25%, which cannot include MMT-8.

Ab315079790.000.25621.20.050.00
Bb7254070750.500.382.21.90.110.07
Cb900075770.250.001.81.30.240.19
D1920059641.631.630.5NA0.140.10
Eb44232067730.750.881.51.20.300.16
Fb090076800.380.004.22.30.100.06
GNA43NA34257NA1.636.85.20.020.22
Hb15014076750.500.50NANA0.160.04
I32113071760.380.381.52.00.000.00
J545311776780.500.501.01.10.060.02
Kb241310377771.380.631.31.30.110.02

The EG improved in 5 VRM in knee extensors by 3.8 kg in the right and left sides, while there was no change in the CG (Table 3). The EG improved compared to the CG in 5 VRM in right knee extensors with a tendency toward between-group difference in the left knee extensor (Table 3). The EG improved in VO2 max (liters/minute−1 and W) compared to the CG (Table 3). The EG also had a small reduction in physician's global disease activity compared to the CG (Table 3).

Improved patient preference and limitations of ADL

A minor improvement was seen in limitations of ADL in the MAP domain moving around in the EG compared to the CG (Table 3). The EG displayed a within-group improvement in patient preference that was not seen in the CG (Table 3).

One-year open extension followup

Patients in both groups remained in a stable disease phase without flares and with only minor changes in pharmacologic treatment. In the EG, 2 patients reduced their daily dose of prednisolone at 52 weeks (from 1.25 to 0 mg and from 5.0 to 3.5 mg). One of these patients increased their azathioprine (AZA) dosage (from 50 to 100 mg/day) due to elevated serum CPK levels (from 5.1 to 23.7 μkat/liter) and another reduced their dosage of AZA (from 100 to 50 mg/day). In the CG, 1 patient increased their prednisolone dosage (from 2.5 to 3.75 mg/day), 1 patient reduced their prednisolone dosage (from 10 to 8.75 mg/day) but increased their dosage of AZA (from 50 to 100 mg/day), and 2 patients reduced their prednisolone dosages (from 3.5 to 2.5 mg/day and from 2.5 to 0 mg/day). Two patients in the EG and 1 in the CG were lost to followup for reasons not related to the intervention or for unknown reasons (Figure 1).

Health

The EG improved in the SF-36 domain general health compared to baseline, while there was a small decline in the domain vitality compared to the CG (Table 5). The CG improved in mental health compared to baseline (Table 5).

Table 5. Changes in health, muscle performance, patient preference, and activities of daily living in the 1-year open extension part of the study from baseline to 52-week followup for the EG and the CG*
Δ in variable (52 weeks vs. baseline)EG (n = 11)CG (n = 10)EG vs. CG, PGroup × time interaction, P
Estimate, mean (95% CI)PEstimate, mean (95% CI)P
  1. EG = exercise group; CG = control group; 95% CI = 95% confidence interval; SF-36 = Short Form 36; 5 VRM = 5 voluntary repetition maximum in knee extensors; MACTAR = McMaster Toronto Arthritis Patient Preference Disability Questionnaire; MAP = Myositis Activities Profile.

  2. a

    Domains of the SF-36 and the MAP with nonsignificant changes are not reported.

  3. b

    Significant at P < 0.05.

SF-36 (scale 0–100)a      
General health10.9 (1.5, 20.4)0.025b9.1 (−1.1, 19.3)0.0790.7900.265
Vitality−4.5 (−14.3, 5.3)0.3625.5 (−5.1, 16.0)0.3060.1720.009
Mental health−1.2 (−7.3, 5.0)0.6877.78 (1.1, 14.5)0.026b0.0530.085
5 VRM right, kg5.7 (3.0, 8.5)< 0.001b1.3 (−3.8, 6.5)0.5990.1310.284
5 VRM left, kg5.7 (3.2, 8.2)< 0.001b0.0 (−4.8, 4.7)0.9840.036b0.077
MACTAR (range 19–39)−3.7 (−7.7, 0.4)0.076−2.2 (−6.5, 2.1)0.3160.6180.344
MAPa      
Work0.0 (−0.8, 0.8)0.9310.1 (−0.7, 1.0)0.7880.7980.030b
Muscle performance

The EG was still improved in knee extensor muscle performance (5 VRM) compared to baseline by 5.7 kg in the right and left legs, whereas the CG was unchanged compared to baseline (Table 5).

There was a between-group difference in favor of the EG in the left leg (Table 5).

Patient preference and limitations in ADL

There was no difference in patient preference assessments compared to baseline in either group (Table 5). There was a decline in ADL (MAP domain work) in the CG compared to the EG; however, it was not clinically relevant (Table 5).

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgments
  9. REFERENCES

In this multicenter RCT study, patients with established PM/DM had improved muscle performance, improved VO2 max, reduced disease activity, and to some extent improved ADL after 12 weeks of endurance exercise. We could also demonstrate improved health, which was strongly related to the improved VO2 max. The improved muscle performance was sustained after 1 year, but other variables were less consistent.

According to our hypothesis regarding the controlled 12-week part of the study, we could demonstrate clinically relevant improved health ([32]). The improvement in the domain physical function is in line with an open-label resistance exercise study ([33]). We also detected an improvement in the domain vitality compared to the CG indicating a positive effect on fatigue, and within-EG improvement in the domain mental health. This indicates a potentially beneficial effect of endurance exercise on fatigue and mental health in PM/DM, as previously shown in other populations ([34, 35]). In addition, there was a strong correlation between VO2 max and health. This might indicate that low VO2 max in established PM/DM contributes to sustained low health observed in these patients, similar to the general population ([4, 5, 9, 10, 36]). Furthermore, we determined that improved health was strongly related to improved VO2 max. We suggest that the increased VO2 max by the endurance exercise could contribute to improved health, as in other populations ([37, 38]).

We hypothesized that the endurance exercise would be beneficial regarding disease activity in established PM/DM. We could demonstrate lower disease activity after the endurance exercise compared to before. Although the changes in disease activity are small and the 20% change proposed by the IMACS group ([31]) might be within the error of measurement, it is worth noting that no CG patients were responders. It is not clear how exercise may reduce disease activity; however, exercise has an antiinflammatory effect via increased circulating antiinflammatory cytokines, including interleukin-1 (IL-1) receptor antagonist, IL-10 ([39]), a decrease in proinflammatory cytokines ([40]), and an increase in IL-6, which is thought to stimulate antiinflammatory cytokines ([41]). Furthermore, exercise-modulated antiinflammatory cytokine changes were detected directly in muscle tissue ([42, 43]). Endurance exercise might be more effective than resistance training to achieve antiinflammatory effects and therefore reduce disease activity ([39]). Our study shows that 7 of 11 patients responded with reduced disease activity, whereas we previously reported that 2 of 8 patients responded following resistance training according to the IMACS criteria ([15]). One suggested mechanism is that endurance exercise resulting in improved VO2 max may activate the vagus nerve and give rise to antiinflammatory activity, thus suppressing cytokine production ([40, 44]). Consistent with this, all EG responders with reduced disease activity were also responders with improved VO2 max.

We also hypothesized that endurance exercise would be beneficial regarding disability in established PM/DM. This was demonstrated by improved muscle performance and VO2 max in the EG compared to the CG. All responders in 5 VRM also improved in VO2 max, indicating that the effects of endurance exercise included both cardiovascular and skeletal muscle adaptations. Also, we showed a minor improvement in ADL not seen in the CG, indicating that endurance exercise seems to improve ADL more than resistance training ([15]). The MACTAR was highly responsive to interventions in rheumatoid arthritis and systemic sclerosis ([45-47]); however, our study could only detect improvement within the EG. The MACTAR improvement exceeded the error of measurement ([22]); however, the clinical relevance of the changes in the MAP (ADL) is more uncertain.

Finally, we hypothesized that a 12-month open extension followup period would display long-term improvement in the EG compared to the CG. This was confirmed regarding the sustained 5 VRM improvement of up to 52 weeks in the EG. However, all other parameters were back to baseline values or even lower, suggesting that the EG did not maintain the high exercise levels after the 12-week intervention ([48]).

There are clear limitations of our study. One is that the patients did not keep exercise diaries during the open extension part of the study. Another weakness is the absence of a 52-week physician's disease activity assessment. Further, we may only generalize our results to other types of physical therapist–supervised endurance exercises performed in the same intensity and duration in established PM/DM. However, due to the relative paucity of men in the EG, the external validity regarding exercise effects in men is limited. Research supports the introduction of supervised low- to moderate-intensity resistance training in active PM/DM after introduction of corticosteroids ([11]). Safety and efficacy of endurance exercise need to be studied in active disease. Despite these limitations, we suggest that a physically active lifestyle including regular endurance exercise is helpful in established PM/DM to maintain health, as in the general population and other diseases ([37, 38]). Professional support for behavioral lifestyle changes seems to be essential in chronic diseases and should be further investigated in patients with PM/DM ([49]).

Patients responded to the endurance training despite various disease damage and disease duration. We recommend endurance exercise to be individually adapted to clinical status and introduced on a lower level with gradually increased intensity under supervision by a physical therapist. Also, a VO2 max test with electrocardiography is suggested before starting endurance exercise to establish safety, especially in patients with heart and lung disease, and to establish correct exercise intensity.

This multicenter RCT study demonstrates that 12 weeks of endurance exercise improves health and may reduce disease activity in patients with established PM/DM. This could potentially be mediated through improved VO2 max. The results also indicate improved muscle performance, VO2 max, and to some extent ADL. The EG had only sustained improvement in muscle performance compared to the study start at 1-year followup, indicating a need for support to change exercise behavior to improve and maintain health in PM/DM patients.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgments
  9. REFERENCES

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Ms Alemo Munters 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. Alemo Munters, Dastmalchi, Esbjörnsson, Alexanderson.

Acquisition of data. Alemo Munters, Dastmalchi, Andgren, Emilson, Bergegård, Johansson, Orefelt Tholander, Hanna, Lidén.

Analysis and interpretation of data. Alemo Munters, Regardt, Alexanderson.

Acknowledgments

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgments
  9. REFERENCES

The authors would like to thank Christina Ottosson for study coordination/data collection and Professor Ingrid E. Lundberg for participation/critical reading of the manuscript.

REFERENCES

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  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgments
  9. REFERENCES
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