Randomized comparison of a multidisciplinary team care program with usual care in patients with systemic sclerosis

Authors


  • ISRCTN: 64237175.

Abstract

Objective

To compare the effectiveness of a multidisciplinary team care program with usual outpatient care in patients with systemic sclerosis (SSc; scleroderma).

Methods

We performed a randomized controlled trial comparing a 12-week multidisciplinary team care program (1 day per week; individual treatments, group exercises, and group education) with outpatient clinic care. Outcome measures included the Hand Mobility in Scleroderma (HAMIS) test, grip strength, maximal mouth opening (MMO), 6-minute walk distance (6MWD), maximum aerobic capacity (VO2max), Checklist Individual Strength 20 (CIS-20), SSc Health Assessment Questionnaire (HAQ), and Short Form 36 (SF-36), assessed at 0, 12, and 24 weeks. Statistical comparisons of change scores were done by analysis of covariance.

Results

Twenty-eight patients were assigned to the intervention group (mean age 53.9 years, 15 of 28 with diffuse SSc) and 25 were assigned to the control group (mean age 51.7 years, 15 of 25 with diffuse SSc). Twenty-five patients (89%) in the intervention group completed the treatment program. At 12 weeks, there was a significantly greater improvement in grip strength (2.2 versus −1.8 kg; P = 0.001), MMO (1.4 versus −0.9 mm; P = 0.011), 6MWD (42.8 versus 3.9 meters; P = 0.021), and HAQ score (−0.18 versus 0.13; P = 0.025) in the intervention group, whereas differences for the other outcome measures did not reach significance. At 24 weeks, the effect on grip strength persisted.

Conclusion

In patients with SSc, a 12-week multidisciplinary day patient treatment program was more effective than regular outpatient care with respect to 6MWD, grip strength, MMO, and HAQ score, but not for VO2max, HAMIS test, CIS-20, SF-36, and visual analog scale for pain. This study provides a first step in quantifying the effect of a multidisciplinary team care program and warrants the conduct of further intervention studies.

INTRODUCTION

Systemic sclerosis (SSc; scleroderma) is an autoimmune disease characterized by fibrosis of multiple organs (1). Two main subtypes are distinguished: limited cutaneous SSc and diffuse cutaneous SSc (dcSSc) (2). Despite improvements in medical treatment, SSc is associated with significant morbidity and mortality (3–6).

To help patients cope with the consequences of the disease, rehabilitative strategies are often provided. Rehabilitation in SSc may include psychoeducational interventions; exercise therapy; the application of physical modalities, assistive devices, and orthoses; joint protection; and energy conservation, dietary interventions, and comprehensive multidisciplinary team care interventions.

Whereas in other rheumatic conditions, especially rheumatoid arthritis (RA), the effectiveness of multidisciplinary team care has been consistently demonstrated (7), in SSc the evidence on comprehensive rehabilitation is scarce (8). A few studies demonstrated a significant improvement of measures of global health and hand function (9, 10), as well as mouth function (10, 11), in patients participating in a rehabilitation program. However, no direct statistical comparisons of the changes in outcome between the intervention group and control group were made. Studies on the effect of single interventions, including patient education (12, 13), aerobic exercise (14), finger (15) or mouth stretching (16), and hand massage and manipulation (17), showed promising results, although most of them (12–16) had a noncontrolled design.

Considering the paucity of data on comprehensive rehabilitative treatment strategies in SSc, this proof-of-concept study was designed to provide preliminary evidence of efficacy of a multidisciplinary treatment team care program on multiple outcome measures reflecting the health status of SSc patients as compared to usual outpatient care.

PATIENTS AND METHODS

Study design.

This randomized controlled clinical trial was conducted from September 2006 until September 2008. Ethical approval was obtained from the Institutional Review Board of the Leiden University Medical Center. The patients' written informed consent was obtained at enrollment. Randomization was performed by an independent administrative assistant by means of a 4-block randomization list, made up with a random-digit generator. Patients were stratified according to the type of SSc (1). Patients allocated to the control group were offered to participate in the multidisciplinary team care program after completion of the final followup assessment.

Patients.

The medical records of SSc patients listed in the SSc registry of our hospital and referrals from other hospitals within the enrollment period were screened for global eligibility by corresponding author (AAS). Inclusion criteria consisted of SSc according to the criteria by LeRoy et al (1), age 18–75 years, being able to cycle on a bicycle ergometer, stable antiinflammatory medication over the past 2 months, and fluency in Dutch. Exclusion criteria were engagement in another exercise therapy program or concomitant diseases interfering with the performance of daily activities.

Patients fulfilling the inclusion criteria were informed about the study and invited for a further screening to judge their exercise tolerance. The screening consisted of history taking, physical examination, and the following additional investigations: blood pressure (at rest), chest radiograph, 24 hours monitoring electrocardiography, Doppler ultrasonography of the heart, exercise test by means of a bicycle ergometer, and pulmonary function testing. All test results were evaluated by a consulting cardiologist (RWCS) and pulmonologist (MKN) and, if necessary, additional examinations were scheduled.

Multidisciplinary team care program (intervention).

The multidisciplinary team care program was delivered at the day patient clinic of the department of rheumatology of a university medical center during 12 consecutive weeks, one day per week. The multidisciplinary team comprised a rheumatologist, an occupational therapist, a physical therapist, a social worker, and a clinical nurse specialist. For every patient, individual treatment goals were set and discussed during 3 weekly multidisciplinary team conferences. The program consisted of standardized group sessions (general exercises, hand/mouth exercises, and educational sessions) and, depending on the patients' individual needs, individual treatments by the rheumatologist and health professionals. In addition, patients were required to participate in individual supervised exercises provided by a physical therapist near their own home in a private practice once a week and to perform a home-based exercise program on at least 6 days per week. The program was delivered to groups with a minimum of 6 points and a maximum of 10 patients (see Supplementary Appendix A, available in the online version of this article at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2151-4658). After completion of the intervention, patients were advised to continue the exercises supervised by the local physical therapist. All other interventions or referrals after the intervention period were left to the treating rheumatologist.

Safety and adherence monitoring of the multidisciplinary team care program.

Safety was monitored by recording all terminations or adaptations of exercise sessions or other components of the treatment program due to pain, exertion, or other reasons; adaptations were made based on a questionnaire evaluating the occurrence of pain during or after training and the time to recovery after each group session. In addition, any alterations in medication in particular analgesics were recorded.

The adherence to the supervised group exercises (general and hand/mouth exercises) in the clinic and the supervised exercises at the private practices was monitored by attendance lists and records of individual progress. For the home-based individual exercises (hand/mouth) a diary was filled in, with weekly evaluation by the physiotherapist in the hospital. Compliance with the group educational sessions was monitored by an attendance list kept by the clinical nurse specialist in the hospital.

Control condition.

Patients in the control group received usual outpatient care provided by their attending rheumatologist. Attending rheumatologists had a free choice with respect to any diagnostic or therapeutic interventions, including referral to a physical therapist, except for referrals to group exercises, group educational programs, or multidisciplinary team care programs.

Assessments.

Assessments took place at baseline, 12 weeks, and 24 weeks, and were done by a trained assessor (FJvdG) blinded for the treatment condition. Sociodemographics, disease characteristics, past/current medications, and modified Rodnan skin score (18) were assessed at baseline.

Recording of individual treatments.

All individual treatments by rheumatologists, physical therapists, occupational therapists, nurses, and social workers in both the intervention and control groups during the duration of the trial were recorded in the medical files by the treating rheumatologists, and for patients in the intervention group also by the clinical nurse specialist.

Outcome measures of effectiveness.

Body functions.

The Hand Mobility in Scleroderma (HAMIS) test consists of 9 items graded on a scale of 0–3, and the final score ranges from 0 (normal function) to 27 (severe immobility). It was found to be a reliable instrument in the evaluation of hand function in SSc (19) and longitudinal assessment of hand mobility in early SSc (20). An average value of the left and right hands was computed.

Grip strength (kg) was measured with a Jamar dynamometer (JA Preston Corporation) (21). After testing twice, the highest score was registered. An average value of the grip strength of the left and right hands was computed.

The maximal mouth opening (MMO) was measured with a digital caliper as the maximal interdental distance. Measurement of the MMO was used in several studies evaluating mouth function in SSc (17, 22).

The 6-minute walk distance (6MWD) evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism (23). It reflects daily exercise and has good construct validity, as demonstrated in SSc patients with pulmonary arterial hypertension.

The maximum aerobic capacity (VO2max), a standard exercise test on an electronically braked cycle ergometer, was performed according to the ATS/ACCP Statement on Cardiopulmonary Exercise Testing (24). At baseline (forehead), pulse oximetry, blood pressure, heart rate, and gas exchanges were recorded. Pulse oximetry and heart rate were monitored during 1 minute of rest, 2 minutes of unloaded cycling at 60 revolutions per minute followed by an increasing load to maximum tolerance, and 3 minutes of recovery. Each exercise test was supervised by a pulmonary physician (MKN). Apart from the VO2max, maximal load, heart rate, and ventilation at the maximal tolerated work rate were monitored.

The Checklist Individual Strength 20 (CIS-20) is a Dutch generic 20-item questionnaire measuring 4 dimensions of fatigue, including fatigue, concentration, impaired motivation, and impaired activity, on a 7-point Likert scale (25). Higher scores indicate a higher degree of fatigue, more concentration problems, reduced motivation, and less activity. The CIS-20 was developed for patients with chronic fatigue syndrome and has good psychometric properties (25).

Functional ability.

The SSc Health Assessment Questionnaire (HAQ) is a 20-item questionnaire comprising 8 domains of activities of daily living, with the final score ranging from 0 (no disability) to 3 (severe disability), and visual analog scales. The SSc HAQ score was calculated using the aids/devices. It has been found to be a reliable outcome measure for disease severity in SSc (26). In addition, a Dutch HAQ translation demonstrated good psychometric properties (27).

Quality of life.

The Short Form 36 (SF-36) is a generic measure of quality of life that can be converted into two summary scales, the physical component summary (PCS) scale and the mental component summary scale, standardized to a mean ± SD score of 50 ± 10 in the general population. For this purpose, we used the scores from an age- and sex-matched normative sample, drawn from a random sample of Dutch adults (n = 1,742) (28), and factor score coefficients (29). The SF-36 has been found to be a reliable outcome measure for disease severity in SSc (26).

Statistical analysis.

The target study sample size was based on the expected improvement of the 6MWD, HAQ score, and PCS scale of the SF-36, since these outcomes are frequently used in rehabilitation studies in other chronic diseases (30–34). At the time of this study design, no information on outcome parameters of other rehabilitation programs in SSc was available. In a noncontrolled study (35), a 12-week exercise program for patients with dermatomyositis resulted in a 30% improvement of the 7-minute walk distance (from 312 meters [range 81–422] to 404 meters [range 124–549]). Assuming a 30% improvement in the intervention group and 0% in the control group, α = 0.05, and β = 0.20 (power of 0.80), 22 patients per group would be needed to detect this difference (n = 7.85 × 0.15[0.85] × 2/[0.3]2). A power calculation based on the PCS scale gave similar results. In a study on a similar rehabilitation program in patients with RA, a 22% improvement of the HAQ score was seen (33). Assuming a 22% improvement in the intervention group and 0% in the control group, α = 0.05, and a power of 0.80, 28 patients per group would be needed to detect this difference (n = 7.85 × 0.11[0.78] × 2/[0.22]2). Based on an average of these calculations, we aimed to enroll 50 patients in the study.

Data entry was performed using Microsoft Office Access 2003. All results were reported according to the Consolidated Standards of Reporting Trials Statement to Randomized Trials of Nonpharmacologic Treatment (36). Analysis was performed by the intent-to-treat principle.

Statistical analyses were executed using SPSS software, version 16.0. Measures with a Gaussian distribution on histogram are expressed as the mean ± SD, and measures with a non–Gaussian distribution are expressed as the median and interquartile range (expressed as the net result of the 75th to 25th percentiles) or the range. In case of more than 20% of missing data for one variable, the group mean value for that variable would be imputed. Descriptive statistics were calculated for all variables, and comparisons of baseline characteristics and numbers of patients using individual treatments were done by a chi-square test, independent t-test, Mann-Whitney U test, or Fisher's exact test, where appropriate. The level of statistical significance (2-sided) was set at P values less than 0.05.

In both the intervention and control groups, the changes in the outcome measures between the baseline and 12-week assessments (change 0–12 weeks) and between the baseline and 24-week assessments (change 0–24 weeks) were assessed with a paired t-test. Comparison of the change scores between the intervention and control groups were done by performing analysis of covariance with correction for baseline values.

RESULTS

Patient inclusion and characteristics.

Ninety-one patients were potentially eligible for the study according to their medical records and were contacted (Figure 1). Sixty patients were interested and took part in the further screening. Fifty-three patients (88%) met the inclusion criteria; 28 participants were randomly assigned to the multidisciplinary team care program, and 25 to the control group. The study was completed by 24 (86%) of 28 patients in the intervention group and by 23 (92%) of 25 patients in the control group (P = 0.671). Reasons for discontinuation were family circumstances and disease progression in the control group, and tendon rupture, painful skin, malignancy, and arthritis in the intervention group.

Figure 1.

Flow diagram of a randomized comparison of a multidisciplinary treatment program with regular outpatient care in patients with systemic sclerosis.

Table 1 shows the demographics and disease characteristics of patients in the intervention and control groups. None of the differences between the groups reached statistical significance.

Table 1. Disease characteristics of 53 SSc patients participating in a randomized controlled trial evaluating the effectiveness of a multidisciplinary team care program as compared to usual care*
 Intervention group (n = 28)Control group (n = 25)P
  • *

    Values are the number (percentage) unless otherwise indicated. SSc = systemic sclerosis; IQR = interquartile range; dcSSc = diffuse cutaneous SSc; MRSS = modified Rodnan skin score; ANA = antinuclear antibody; ESR = erythrocyte sedimentation rate; CRP = C-reactive protein; FVC = forced vital capacity; DLCO =diffusing lung capacity for carbon monoxide.

  • By chi-square test, Student's t-test, Mann-Whitney U test, or Fisher's exact test, where appropriate.

Female sex19 (67.9)21 (84.0)0.297
Age, mean ± SD years53.9 ± 10.851.7 ± 10.80.459
Disease duration, median (IQR) years6.5 (8.2)8.2 (10.5)0.708
dcSSc disease subset15 (53.6)15 (60.0)0.846
Onset of Raynaud's phenomenon, median (IQR) months8.6 (12.7)10.3 (12.9)0.694
MRSS (range 0–51), mean ± SD5.0 ± 4.05.2 ± 6.20.865
Autoantibodies, positive   
 ANA26 (92.9)23 (92.0)1.000
 Anti–Scl-7010 (35.7)10 (40.0)0.878
 Anticentromere3 (10.7)5 (20.0)0.335
ESR, median (IQR) mm/hour14.0 (19.0)20.5 (30.0)0.059
CRP level, median (IQR) mg/liter3.0 (3.0)5.0 (7.5)0.159
Interstitial lung disease13 (46.4)12 (48.0)1.000
Cardiac involvement5 (17.9)2 (8.0)0.426
FVC, mean ± SD % predicted91.0 ± 21.995.0 ± 21.10.994
DLCO, mean ± SD % predicted61.4 ± 17.561.3 ± 18.10.498
Current treatment   
 Methotrexate4 (14)2 (8)0.472
 Prednisone4 (14)1 (4)0.201
 Azathioprine2 (7)2 (8)0.632
Previous treatment   
 Cyclophosphamide7 (25.0)7 (28.0)0.920
 Stem cell transplantation6 (21.4)4 (16.0)0.472
 Methotrexate8 (28.6)9 (36.0)0.831
 Prednisone7 (25.0)6 (24.0)1.000

Individual treatments in the intervention and control groups.

Table 2 shows the numbers of patients receiving individual treatments provided by the rheumatologist and health professionals in both groups. For the rheumatologist and all health professionals, significantly more patients in the intervention group received individual treatments.

Table 2. Numbers of patients receiving individual treatments provided by the rheumatologist and rheumatology health professionals during the 12-week intervention period, 12 weeks thereafter, and the total period of 0–24 weeks
 Intervention group (n = 28)Control group (n = 25), 0–24 weeks, ≥1 consultationP*
Baseline, initial assessment0–12 weeks, ≥1 consultation12–24 weeks, ≥1 consultation0–24 weeks, ≥1 consultation0–24 weeks, initial assessment excluded, ≥1 consultation
  • *

    Comparisons (chi-square test or Fisher's exact test) of numbers of patients receiving individual treatments in the intervention and control groups over 0–24 weeks (initial assessment of the intervention group excluded).

  • All 28 patients in the intervention group received individual general exercise therapy (12 sessions) at a private practice during the intervention period of 0–12 weeks plus, if needed, individual physical therapy sessions at the clinic, depending on individual health status.

Rheumatologist2821182826170.030
Physical therapist2828282828100.000
Occupational therapist28223282210.000
Social worker28174281720.000
Clinical nurse specialist28282282840.000

Adverse effects and adherence to the multidisciplinary intervention.

Two patients in the intervention group had adverse effects related to the treatment program. One experienced progressively painful skin in 3 weeks of participation, resulting in discontinuation of the program. An increased thickening or inflammation of the skin was not seen. The other patient experienced an Achilles tendon rupture during the circuit training in the second week. One patient discontinued the intervention prematurely because of an osteosarcoma requiring surgical intervention. During the bicycle training, 6 patients in the intervention group trained with an intensity lower than 60% of the specific maximum heart rate because of pain (diagnosis of osteoarthritis: n = 4, exertion: n = 2). Changes in the use of analgesics were not seen during the program for any of the patients in the intervention group.

Of the 25 patients completing the program, 20 (80%) attended 10 or more of both the 12 supervised group exercise (general) sessions and the 12 supervised group exercise (hand/mouth) sessions. For the supervised sessions, 21 patients (84%) attended 10 or more of the 12 scheduled individual exercise sessions at the private practices. Twenty-one (84%) of the patients performed their exercise of the hand/mouth on at least 5 days of the recommended 6 days per week. Twenty-three patients (92%) attended 5 or more of the 6 group educational sessions.

End points of effectiveness.

Less than 20% of values were missing at any time point and the missing data were completely at random for all of the end point variables, so no imputation of data was employed. Table 3 shows the baseline values and change scores of all outcome measures. At 12 weeks, the improvement of grip strength, MMO, 6MWD, and the HAQ score was significantly greater in the intervention group than in the control group. The changes of the other outcomes were comparable between the groups.

Table 3. End points of body functions, functional ability, and quality of life in 53 patients with SSc participating in a randomized controlled trial evaluating the effectiveness of a multidisciplinary team care program*
 BaselinePChange 0–12 weeks, mean (95% CI)PChange 0–24 weeks, mean (95% CI)P
  • *

    SSc = systemic sclerosis (scleroderma); 95% CI = 95% confidence interval; HAMIS = Hand Mobility in Scleroderma; 6MWD = 6-minute walk distance; CIS-20 = Checklist Individual Strength 20; HAQ = Health Assessment Questionnaire; SF-36 = Short Form 36; PCS = physical component summary; MCS = mental component summary; VAS = visual analog scale.

  • Intervention and control group values compared.

  • Multiple linear regression comparison of change between the intervention and control groups.

  • §

    P < 0.05.

  • Maximal oxygen uptake during bicycle exercise test.

Body functions      
 HAMIS test, mean ± SD 0.449 0.163 0.038§
  Intervention6.8 ± 5.4 −1.2 (−2.2, −0.3)§ −1.6 (−2.7, 0.4) 
  Control5.7 ± 3.9 −0.2 (−1.1, 0.7) 0.2 (−1.0, 0.6) 
 Grip strength, mean ± SD kg 0.882 0.001§ 0.044
  Intervention26.2 ± 12.4 2.2 (0.6, 3.8)§ 2.6 (0.9, 4.2) 
  Control26.7 ± 10.3 −1.8 (−3.4, −0.1)§ −0.4 (−2.7, 2.0) 
 Mouth opening, mean ± SD mm 0.632 0.011§ 0.004§
  Intervention36.5 ± 9.3 1.4 (0, 2.8)§ 1.4 (−0.3, 3.0) 
  Control37.6 ± 6.6 −0.9 (−2.1, 0.5) −0.4 (−1.5, 0.7) 
 6MWD, mean ± SD meters 0.472 0.021§ 0.280
  Intervention499.9 ± 107.2 42.8 (22.1, 63.6)§ 34.8 (7.9, 61.8)§ 
  Control520.6 ± 94.2 3.9 (−20.8, 28.5) 12.0 (−13.1, 37.1) 
 O2 uptake, mean ± SD 0.645 0.201 0.745
  Intervention20.4 ± 5.1 1.1 (−0.3, 2.6) 1.1 (−0.9, 3.2) 
  Control21.1 ± 5.7 −0.1 (−1.2, 1.0) 0.6 (−0.9, 2.1) 
 CIS-20, mean ± SD 0.172 0.189 0.429
  Intervention74.2 ± 27.6 −13.4 (−20.9, −5.9)§ −7.8 (−16.3, 0.8) 
  Control84.0 ± 18.5 −7.9 (−19.6, 3.9) −5.7 (−13.4, 2.1) 
Functional ability      
 SSc HAQ score, mean ± SD 0.632 0.025§ 0.255
  Intervention0.81 ± 0.66 −0.18 (−0.36, −0.01)§ −0.26 (−0.51, 0)§ 
  Control0.73 ± 0.46 0.13 (−0.02, 0.27) −0.1 (−0.24, 0) 
Quality of life      
 SF-36 PCS scale, mean ± SD 0.251 0.074 0.675
  Intervention41.3 ± 11.4 2.1 (−1.5, 5.7) −0.7 (−3.7, 2.4) 
  Control37.6 ± 10.4 −0.5 (−4.4, 3.4) 1.4 (−2.4, 5.1) 
 SF-36 MCS scale, mean ± SD 0.662 0.906 0.677
  Intervention51.9 ± 7.5 0 (−2.9, 2.9) 1.9 (−1.2, 5.0) 
  Control50.9 ± 7.4 0.6 (−3.2, 4.3) 1.6 (−2.3, 5.5) 
 VAS for pain, mean ± SD mm 0.642 0.053 0.465
  Intervention27.0 ± 27.7 −5.7 (−14.2, 2.7) −2.1 (−11.2,7.1) 
  Control30.6 ± 25.5 5.9 (−5.0, 16.8) 1.2 (−11.5, 13.9) 

At 24 weeks, this significance was sustained for the MMO.

DISCUSSION

This proof-of-concept randomized controlled trial shows that a 12-week day patient multidisciplinary program resulted in a greater improvement of grip strength, MMO, 6MWD, and HAQ score than regular outpatient care. Although differences were still present at 24 weeks, the significance of most of them was not sustained. No differences were seen for VO2max, HAMIS test, CIS-20, SF-36, and visual analog scale for pain.

The results of previous evaluations of comprehensive rehabilitation programs in SSc are similar to our study with respect to significant improvements in mouth opening (10, 11, 17), hand function (9, 10), and overall functional ability (10). The mean increase of MMO in our patients was considerably less than in two other studies (10, 17). However, compared with these studies, the patients in our study had less impairment: 8% had a normal MMO (>50.0 mm) and 36% had an MMO >40.0 mm (22), making an overall group improvement more difficult to achieve. The hand exercises in our program resulted in a moderate decrease of the HAMIS test as compared to 20 patients completing a 9-week rehabilitative treatment (mean ± SD 6.8 to 5.6 ± 1.2 versus 11.4 to 7.0 ± 4.4) (16). This difference may also be explained by a lower level of baseline hand disability in our patients and the different type of intervention.

In both previous studies (9, 10), an improvement of quality of life was seen. Although our study showed a greater improvement of overall physical health in the intervention group as compared to the control group, the difference did not reach significance. The significant improvement of the 6MWD and HAQ score but not of the SF-36 PCS scale suggests that these outcome measures may reflect different dimensions of physical functioning. This is in line with a study by Khanna et al (26) on the responsiveness to change of the HAQ Disability Index (DI) compared with the SF-36 in patients with dcSSc. The HAQ DI had a larger magnitude of responsiveness if clinical measures were considered, while the SF-36 had a larger magnitude of responsiveness in relation to changes in overall disease activity (patient and physician global assessment). On the other hand, Antonioli et al (9) found a statistically significant improvement of both of the SF-36 subscales after a 2-week rehabilitation program. In the absence of a gold standard to measure the effect of rehabilitation interventions in SSc, we employed different end point measures. In this respect, this trial should be considered as a proof-of-concept study, with its results warranting further research.

Comparisons among studies are hampered by a number of differences. With respect to the intervention, previous studies had a strong focus on physical therapy interventions (9, 10, 14, 16). Maddali Bongi et al (10) used a 9-week tailored rehabilitation program with education, mostly passive treatment of the hand and face, and a general exercise program, both for one hour once a week. The 2-week program with exercise therapy and physical modalities by Antonioli et al (9) had a shorter duration, but was followed by at-home exercises. In the present study, more health care professionals were involved and a greater variety of treatments was provided, including group education and individual interventions tailored to patients' needs. A similar multidisciplinary team care model as employed in the present study was found to be effective in patients with RA (33, 37). Second, the two previous studies (10, 11) used other outcome measures. Third, a direct statistical comparison was not made between the intervention and control groups in either of the two previous studies, so that the changes reported cannot be interpreted as treatment effects. Finally, there were differences in the baseline characteristics of the patients. In general, it can be assumed that in patients with less disability, an improvement of disability is more difficult to achieve. In SSc, a classification of the HAQ has been proposed into no to mild disability (range 0.00–1.00), moderate disability (range 1.01–2.00), and severe disability (range 2.01–3.00) (38). Using this classification, participants in our study (HAQ score of 0.81) and the study by Antonioli et al (HAQ score of 0.63) (9) had mild disability, and in the study by Maddali Bongi, participants had moderate disability (HAQ score of 1.2).

Exercise performance in SSc may be limited because of circulatory, pulmonary, or joint–muscle impairment (39). There are two studies available on exercises aiming to improve exercise tolerance in SSc. A 2-week rehabilitation including lower extremity exercises showed no improvement of the 6MWD (9), whereas our program resulted in a mean improvement of 42.8 meters (8.5%), probably due to the longer duration of our supervised training. An 8-week program with moderate-intensity aerobic exercise (14) resulted in a significant improvement of VO2max in 7 patients with SSc, whereas in our study no improvement of the peak VO2max was seen. This discrepancy may be due to the fact that almost half of the patients in our study had interstitial lung disease (ILD); an improved 6MWD, but not VO2max, was found after physical training for people with ILD (40). Unfortunately, the number of participating patients in this study did not permit subgroup analysis for patients without ILD. The benefits of dynamic exercise have been documented in conditions such as dermatomyositis and polymyositis (41), systemic lupus erythematosus (42), and RA (43). Moreover, it is considered appropriate to include patients with ILD in pulmonary rehabilitation (34), despite the absence of improved VO2max.

Although the improvement of most outcomes was still present at 24 weeks, the effect was not sustained. This is in line with literature on rehabilitation outcomes in SSc (10), ILD (34), and RA (43), underlining the importance of continued exercises and physical activity incorporated in a patient's daily life. This is substantiated by the study the Antonioli et al (9): the 2-week program was followed by home exercises, patients were asked to keep a dairy of activities, and patients were regularly asked for compliance, resulting in an increasing improvement of quality of life as measured by the SF-36 after 2 and 4 months. These results suggest that by promoting lifelong exercises and physical activity as a part of the standard treatment in SSc, health care providers may contribute to sustained improvement of physical functioning and quality of life.

The dynamic exercise program as employed in the present study appeared to be safe and well tolerated by the majority of SSc patients. However, considering the Achilles tendon rupture in one patient despite stretching in advance, extra attention should be paid to warming up. One patient ended participation because of painful skin, without visible skin inflammation. Whether this painfulness was due to increased inflammation is unclear. Increased anti–interleukin-6 and circulating leukocytes were demonstrated in SSc patients after exercise testing (44). In healthy subjects, participation in regular exercise (i.e., training) can reduce basal or resting levels of many inflammatory markers (45). In RA patients, 12 weeks of progressive resistance exercises did not lead to the biologically important alterations in immune response after an acute bout of exercise as compared to healthy controls (46). Finally, no signs of increased inflammation were seen in a muscle biopsy sample in 9 patients with polymyositis/dermatomyositis after 7 weeks of training (41).

Concerning the educational part of the program, similar programs have been described (12, 13) and were found to be well appreciated by SSc patients. The effectiveness of patient education on coping, depression, or illness perception has not yet been established. Our program did not result in improvement of mental status, probably because in our study patients had impairment of physical rather then mental health. A number of studies, however, have described a high prevalence of depressive symptoms (6), pain (47), and body image dissatisfaction in SSc (48). In RA, tailored cognitive–behavioral therapy only offered to patients with a high psychosocial risk profile was effective in reducing depression and fatigue (49). Cognitive–behavioral or other psychosocial interventions have not yet been evaluated in SSc, but they could gain effectiveness if offered to patients with a high-risk profile.

Our study has several limitations. First, the sample size did not permit subgroup analysis to identify patients with the greatest benefits. Mugii et al (15) illustrated that early dcSSc patients would benefit more from range of motion exercises than patients in later stages. In our study, most of the participating patients with dcSSc had nonactive SSc with a longer disease duration. As previously discussed, it is likely that ILD also determines outcome in rehabilitation interventions. Second, our program focused on improving physical functioning more than on mental functioning. Third, in case of a multidisciplinary approach, it is difficult to establish which team care component contributes most to the treatment effect. More knowledge on the effects of single techniques can be obtained by comparing different rehabilitation strategies.

AUTHOR CONTRIBUTIONS

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. Dr. Schouffoer 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. Schouffoer, Ninaber, Beaart-van de Voorde, van der Giesen, de Jong, Stolk, Scherptong, van Laar, Schuerwegh, Vliet Vlieland.

Acquisition of data. Schouffoer, Ninaber, Beaart-van de Voorde, van der Giesen, Stolk, Scherptong, Schuerwegh.

Analysis and interpretation of data. Schouffoer, Ninaber, van der Giesen, Stolk, Voskuyl, Scherptong, Huizinga, Vliet Vlieland.

Acknowledgements

We thank the patients for their efforts and cooperation, the multidisciplinary team of Rheumatology Clinic Sole Mio for developing the day care program, and Atos Medical, Zoetermeer, The Netherlands, for kindly providing a Therabite device for a number of patients taking part in the intervention.

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