- Email: [email protected]
Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort
G Model BONSOI-4253; No. of Pages 6
ARTICLE IN PRESS Joint Bone Spine xxx (2015) xxx–xxx
Available online at
ScienceDirect www.sciencedirect.com
Original article
Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort Cécile Escalas a , Marie Dalichampt b , Maxime Dougados c , Serge Poiraudeau a,∗,b a Department of Physical Medicine and Rehabilitation, AP–HP, Paris Descartes University, Cochin Hospital, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France b Inserm U1153 and IFR Handicap, Cochin Hospital, 75014 Paris, France c Inserm U1153, Clinical epidemiology and biostatistics, Department of Rheumatology, Cochin Hospital, AP–HP, Paris Descartes University, PRES Sorbonne Paris-Cité, 75014 Paris, France
a r t i c l e
i n f o
Article history: Accepted 7 May 2015 Available online xxx Keywords: Axial spondyloarthritis Physical therapy Treatment and epidemiology
a b s t r a c t Objective: To evaluate the effect of physiotherapy on functional limitation in an observational cohort of early axial spondyloarthritis. Methods: Design: prospective population-based cohort study. Patients: 708 patients with early axial spondyloarthritis between 2007 and 2010 naive of TNF blockers. Intervention: early physiotherapy defined by at least eight supervised sessions of physical therapy during the first six months. Measurements: the primary outcome was functional improvement defined by a relative improvement of at least 20% in BASFI at six months. Secondary outcomes were improvement in BASFI at one and two years and ASAS20 response criteria at six months. Statistical analysis: a propensity score of having physiotherapy was developed and multivariate analysis using propensity score weighting were used to assess the effect of physiotherapy on outcome. Results: Overall, 166 (24%) patients had physiotherapy during the first six months. After using propensity score weighting, there was no functional improvement on the primary outcome in patients treated with early physical therapy (relative risk [IC95%]: 1.15 [0.91–1.45]). No differences were observed on secondary outcomes (relative risk [IC95%]: 0.94 [0.80–1.11]). Conclusions: It seems there is no functional benefit for patients with early spondyloarthritis to be treated early by physiotherapy in daily practice, even though the efficacy of physiotherapy has been shown in several randomized controlled studies. © 2015 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
1. Introduction Axial spondyloarthritis (SpA) is a chronic inflammatory rheumatic disease most commonly affecting the axial skeleton, which historically has been difficult to treat. SpA starts commonly early in life and can lead to severe damage of spine with functional impairment, disability and poor quality of life [1,2]. Physical therapy seems to play an important role in the management of patients with SpA. The primary aim of exercise treatment is to avoid stiffening in a flexed position and to improve functional capacity and quality of life. Several randomized controlled trials have demonstrated that physical therapy with various modalities has positive effects on pain and function in SpA [3–7]. The recent recommendations emphasize that non-pharmacological treatment
∗ Corresponding author. E-mail address: [email protected] (S. Poiraudeau).
of SpA should include regular exercise and that individual and group physical therapy sessions should be considered [8,9]. Physiotherapy should be started as soon as SpA is diagnosed and lifelong regular exercises are the mainstay of the treatment [10]. A combined regime of inpatient spa-exercise therapy followed by group physiotherapy is recommended for the highest benefit, and group physiotherapy is also superior to home exercise; the conventional protocols of physiotherapy, including flexibility, stretching and breathing exercises, as well as pool and land-based exercises are recommended. The review by Zochling et al. [11] and a recent systematic review [12] showed that exercises have positive effects on BASFI, BASDAI, pain and mobility function. A Cochrane review on the role of physiotherapy interventions in SpA also concluded that physical therapy (physiotherapy, home exercises, spa therapy) is beneficial [13]. However, small numbers of participants in many trials, heterogeneity of the interventions and outcomes measures and deficiency in reporting data result in wide intervals and lack of strong
http://dx.doi.org/10.1016/j.jbspin.2015.05.008 1297-319X/© 2015 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Escalas C, et al. Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.05.008
G Model BONSOI-4253; No. of Pages 6
ARTICLE IN PRESS C. Escalas et al. / Joint Bone Spine xxx (2015) xxx–xxx
2
evidence. Moreover, it is not clear which treatment protocol and when during the evolution of the disease should be recommended. Finally, no study reporting the effectiveness of physical therapy for SpA in real-life conditions have been published and there could be a substantial gap between physical therapy performed in randomized controlled trials and in daily practice. Moreover, all trials have been conducted in patients who fulfilled New York modified criteria, i.e. who had structural damage of the sacroiliac, and in an advanced stage of their disease. But to our knowledge, no study has reported the effect of physiotherapy in patients with early SpA or without radiographic damage. However, some data suggest that management in early stage of the disease could be decisive [14,15]. “Devenir des Spondylarthropathies Indifférenciées Récentes” (DESIR) is a prospective longitudinal cohort involving 25 rheumatology centres and 708 patients with recent (≤ 3 years) inflammatory back pain suggesting a diagnosis of SpA [16]. These patients can receive any treatment in accordance with their rheumatologist’s decision. Therefore, this cohort represents a unique opportunity to evaluate the current practice and the effect of physiotherapy in real-life conditions. Our main objective was to assess whether physiotherapy delivered in a primary care setting improves function in patients with early inflammatory back pain suggesting a diagnosis of SpA. 2. Methods 2.1. Patients A total of 708 patients with early inflammatory back pain have been included in the DESIR cohort between October 2007 and April 2010 in 25 regional centres in France, with visits scheduled every 6 months during 2 years [16]. Consecutive patients aged > 18 years and < 50 years with inflammatory back pain for more than 3 months and less than 3 years and symptoms suggestive of SpA according to the rheumatologists’ assessment were included in the DESIR cohort. Patients had to fulfil either the Calin or Berlin criteria [17,18]. Patients with a definite diagnosis of non-SpA back pain, conditions that might interfere with the validity of the informed consent and/or prevent an optimal compliance (e.g., alcoholism, psychiatric disorders) and a history of TNF␣ blocker usage were excluded. 2.2. Intervention At each visit in the DESIR cohort, patients reported the number of sessions and the reason for physical therapy. The number of sessions for each patient per 6 months was used to compare patients who had or had not physical therapy. Early physiotherapy was defined as at least 8 supervised sessions of physical therapy in the first 6 months. The optimal number of sessions is unknown and seems to vary between 6 and 10 according to the studies in rheumatic disease. The number of 8 treatment sessions was chosen because this is the number usually accepted to be efficient in daily practice and it corresponds to the number of sessions in studies reporting effect of physiotherapy [19]. Regular physiotherapy was defined as at least 8 supervised sessions of physical therapy in at least 3 periods of 6 months during the first 24 months. 2.3. Measurements The primary outcome measure was an improvement in the patient functional limitation. The Bath Ankylosing Spondylitis Functional Index (BASFI) is a validated self-assessment tool that determines the degree of functional limitation in SpA patient using a 100 mm visual analog scale measuring level of ability with activities in the last 48 h [20]. Functional improvement was defined as a
relative improvement of at least 20% in BASFI, which corresponds to the definition of minimum clinically important improvement in function in rheumatic disease [21] and with the 20% improvement response according to the criteria of the Assessment in Ankylosing Spondylitis (ASAS) International Working Group (ASAS 20 responders) usually used in SpA [22]. Functional improvement was evaluated at 6 months. Secondary endpoints were improvement in BASFI at one and two years. 2.4. Statistical analysis 2.4.1. Descriptive analysis The percentage of patients having physiotherapy and its 95% confidence interval and the number of sessions were evaluated at each intermediate follow-up visit (e.g. 6, 12, 18 and 24 months). Baseline characteristics of patients were compared: qualitative variables were compared with the Chi2 test (Fischer’s exact test when appropriate) and quantitative variables with one-way analysis of variance (ANOVA) (Mann-Whitney U-test when appropriate). 2.4.2. Effect of physiotherapy The effect of early physiotherapy was evaluated as follows. Study outcomes were estimated as part of a linear model using generalized estimating equations. A binomial distribution and log-link function were chosen for the binary criteria to assess relative risks in the context of frequent outcomes. When a convergence problem occurred, a Poisson distribution was used. The variance-covariance matrix was postulated by a symmetrical composition so a constant correlation between two patients in the same hospital could be considered. A Markov chain Monte Carlo method of multiple imputations was used to impute missing data. Five samples imputed were used and variables with more than 20% of missing data were excluded. To take into account the bias in treatment assignment in observational studies, a propensity score method was applied [23]. Formally, the propensity score is the probability of receiving a particular treatment conditional on the individual’s covariate values at baseline. Expecting differences between patients who had or had not physical therapy, a propensity score was used as the probability that a patient with specific baseline characteristics would have physical therapy. Potential confounders at baseline, including all demographic, clinical, radiological and biological data, were selected with automatic stepwise selection procedure in a logistic regression model for each imputed sample to construct the final propensity score model. The propensity score model calibration (Hosmer-Lemeshow goodness-of-fit test) and discrimination performance (area under the receiver operating curve) were evaluated on each imputed sample. A standardized mortality ratio propensity score weight was then used. Patients in the physical therapy group received a weight of 1 and those in the non physical therapy group received a weight of pi/(1−pi) where pi refers to an individual’s probability of having early physiotherapy. Using these weights allowed to estimate the average treatment effect in the treated group (ATT) [24]. The propensity score weights were then incorporated as weights into a generalized linear model with only the physical therapy group as a predictor variable and no covariate. Biases from extreme weights were adjusted by using trimming technique that trims the stabilized weights within a specific range [25]. The balance in baseline risks factors was evaluated in the original and the weighted population by computing the standardized differences. The adequate balance was considered achieved for standardized difference < 10%. At the end, relative risks were estimated with 3 models: the crude model, a classical covariate-adjusted generalized linear model and the propensity model. For each model, the significance level was set at 5%. For propensity analysis, trimming cutpoint with the best balance properties was chosen as main analysis and analyses with
Please cite this article in press as: Escalas C, et al. Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.05.008
G Model BONSOI-4253; No. of Pages 6
ARTICLE IN PRESS C. Escalas et al. / Joint Bone Spine xxx (2015) xxx–xxx
3
Table 1 Baseline patient characteristics according to physiotherapy status in the first 6 months. All patients (N = 689)
Patients without physiotherapy in the first 6 months (N = 523)
Patients with physiotherapy in the first 6 months (N = 166)
P
Age, mean (SD), year Female gender, n (%) Graduate studies, n (%) Missing workdays, median (IQR) BMI, mean (SD), kg/m2
33.3 (8.6) 371 (53.8%) 409 (59.7%) 5 [0–30] 23.9 (4.1)
33.0 (8.8) 258 (49.3%) 308 (59.3%) 3.5 [0–21] 24.1 (4.1)
34.5 (8.0) 113 (68.1%) 101 (60.8%) 10 [0–50] 23.4 (3.8)
0.0486 < 0.0001 0.7319 0.0007 0.0434
Duration of axial symptoms, mean (SD), month Intensity of axial pain, mean (SD) Peripheric joint involvement, n (%) Current clinical manifestations Thoracic pain, n (%) Lumbar pain, n (%) Buttock pain, n (%) BASDAI, mean (SD) BASMI, mean (SD) BASFI, mean (SD) HAQ, mean (SD) SF 36–MCS, mean (SD) SF 36–PCS, mean (SD) ASQol, median (IQR) ASDAS, mean (SD) NSAID intake, n (%) DMARD intake, n (%)
18.5 (10.6) 5.0 (2.7) 395 (57.3%)
18.6 (10.6) 4.8 (2.7) 292 (55.8%)
18.1 (10.9) 5.5 (2.5) 103 (62.0%)
0.5644 0.0042 0.1583
393 (57.0%) 623 (90.4%) 511 (74.2%) 44.9 (20.0) 2.4 (1.0) 30.6 (22.9) 0.67 (0.52) 40.1 (11.2) 39.9 (9.3) 10.0 [5.0–14.0] 2.5 (1.0) 636 (92.3%) 89 (12.9%)
273 (52.2%) 467 (89.3%) 380 (72.7%) 43.4 (20.3) 2.3 (1.0) 29.7 (23.2) 0.64 (0.52) 40.9 (11.3) 40.9 (9.3) 9.0 [5.0–13.0] 2.5 (1.0) 482 (92.2%) 69 (13.2%)
120 (72.3%) 156 (94.0%) 131 (78.9%) 49.7 (18.4) 2.6 (1.1) 33.7 (21.7) 0.79 (0.51) 37.8 (10.9) 37.0 (8.6) 11.5 [8.0–15.0] 2.6 (1.0) 154 (92.8%) 20 (12.0%)
< 0.0001 0.0740 0.1085 0.0004 0.0032 0.0507 0.0012 0.0026 < 0.0001 0.0001 0.1023 0.7971 0.7016
Tender joint count, mean (SD) Swollen joint count, mean (SD) Chest expansion, mean (SD) Schober, mean (SD)
4.3 (8.6) 0.15 (0.83) 6.0 (4.7) 3.8 (1.6)
3.8 (8.0) 0.12 (0.71) 6.1 (5.3) 3.8 (1.6)
5.8 (10.1) 0.22 (1.12) 5.6 (2.0) 3.6 (1.7)
0.0100 0.1816 0.1741 0.1228
HLAB27+, n (%) CRP, mean (SD) Sacroiliac joint structural damage at plain X-Rays, n (%) Sacroiliitis at pelvic MRI, n (%)
400 (58.1%) 8.1 (13.6) 336 (49.5%)
311 (59.6%) 8.1 (12.6) 71 (43.8%)
89 (53.6%) 8.2 (16.4) 265 (51.3%)
0.1749 0.9095 0.0988
228 (33.9%)
48 (29.6%)
180 (35.2%)
0.1898
BMI: Body mass index; BASDAI: Bath ankylosing spondylitis disease activity index; BASMI: Bath ankylosing spondylitis metrology index; BASFI: Bath ankylosing spondylitis functional index; HAQ: Health assessment questionnaire; SF36-MCS: Short form (36) mental component summary; SF36-PCS: Short form (36) physical component summary; ASQol: Ankylosing spondylitis quality of life; ASDAS: Ankylosing spondylitis disease activity score; NSAID: Non-steroidal anti-inflammatory drug; DMARD: Disease modifying anti-rheumatic drug; CRP: C-reactive protein.
others trimming cutpoints were presented as sensitivity analyses. Others sensitivity analyses were conducted using a cut off of 50% to define improvement of functional limitation. Finally, a secondary analysis was performed with the same methodology to estimate the effect of regular physiotherapy (at least 8 supervised sessions of physical therapy in at least 3 periods of 6 months during the first 24 months) on functional improvement (relative improvement of at least 20% in BASFI) at 2 years. Statistical analysis was carried out with SAS software, version 9-1 (SAS Institute Inc., Cary, NC, USA). 3. Results 3.1. Characteristics of the population In total, 689 patients were analysed. Baseline characteristics of the population and comparison between patients who had or had not physiotherapy in the first 6 months are presented in Table 1. At inclusion, 514 (74.6%) patients fulfilled the ASAS criteria for axial SpA. According to inclusion criteria in the DESIR cohort, this population was characterised by young age (mean age 33.3 ± 8.6 years) and short duration of axial symptoms (mean 18.5 ± 10.6 months); 53.8% were women. Patients had high disease activity with a mean BASDAI of 44.9 (± 20.0) and a mean CRP of 8.1 (± 13.6). The mean BASFI was 30.6 (± 22.9) and the mean HAQ was 0.67 (± 0.52). HLAB27 was positive in 58.1% of the patients, 49.5% had sacroiliac joint structural damage at plain X-Rays and 33.9% sacroiliitis at pelvic MRI. Characteristics between patients who had or had not physiotherapy in the first 6 months were generally
comparable, except for sex, intensity of axial pain, presence of thoracic pain, BASDAI and quality of life index. Patients with physiotherapy tended to be more frequently women, to have more sick leaves, to have a higher level of disease activity and a worse quality of life.
3.2. Frequency of physiotherapy In all, 166 (24%) patients had physiotherapy during the first 6 months. The percentage of patients with physiotherapy during each period of 6 months decreased slowly, respectively 22%; 18% and 18% between 6 months and 12 months; 12 months and 18 months and 18 months and 24 months. Between inclusion and 6 months, the mean number of sessions of physiotherapy in the whole group was 7.4 (± 13.2) and the mean number of sessions in patients with physiotherapy was 23.1 (± 14.2). Among the 661 patients who went to at least 3 follow-up visits in the first 2 years, 271 (41%) had at least one period of 6 months with 8 sessions of physiotherapy and 88 (13%) had regular physiotherapy (8 sessions in at least 3 periods of 6 months in the first 2 years).
3.3. Propensity models The most accurate propensity model included 16 variables, including: • demographics data (e.g. sex, change of job, sick leaves);
Please cite this article in press as: Escalas C, et al. Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.05.008
G Model
ARTICLE IN PRESS
BONSOI-4253; No. of Pages 6
C. Escalas et al. / Joint Bone Spine xxx (2015) xxx–xxx
4 Table 2 Prognostic factors for improvement in BASFI at 6 months.
All patients (N = 637)
Patients without improvement in BASFI (N = 317)
Patients with improvement in BASFI (N = 320)
P
Age, mean (SD), year Female gender, n (%) Graduate studies, n (%) Disability status, n (%) Tobacco use, n (%) Alcohol excess, n (%) BMI, mean (SD), kg/m2
33.4 (8.6) 347 (54.5%) 387 (60.9%) 26 (4.1%) 223 (35.2%) 94 (14.9%) 23.9 (4.1)
33.8 (8.6) 190 (59.9%) 180 (57.1%) 20 (6.3) 121 (38.3%) 45 (14.3%) 24.1 (4.2)
32.9 (8.7) 157 (49.1%) 207 (64.7%) 6 (1.9) 102 (32.2) 49 (15.5%) 23.7 (3.9)
0.2294 < 0.0059 0.0514 0.0047 0.1073 0.6668 0.1939
Duration of axial symptoms, mean (SD), month Peripheric joint involvement, n (%) Intensity of axial pain, mean (SD) BASDAI, mean (SD) BASFI, mean (SD) HAQ, mean (SD) SF 36-MCS, mean (SD) SF 36-PCS, mean (SD) BASMI, mean (SD) ASDAS, mean (SD) NSAID intake, n (%) DMARD intake, n (%)
18.6 (10.6) 364 (57.1%) 4.9 (2.7) 44.8 (20.1) 30.3 (22.8) 0.67 (0.52) 40.2 (11.3) 40.0 (9.4) 2.4 (1.0) 2.5 (1.0) 588 (92.3%) 81 (12.7%)
19.5 (10.5) 178 (56.2%) 5.0 (2.7) 45.5 (20.5) 29.0 (22.6) 0.68 (0.52) 39.2 (11.1) 39.9 (9.1) 2.4 (1.0) 2.5 (1.0) 290 (91.5%) 43 (13.6%)
17.7 (10.7) 186 (58.1%) 4.9 (2.7) 44.1 (19.6) 31.7 (22.9) 0.65 (0.52) 41.2 (11.5) 40.1 (9.6) 2.4 (1.0) 2.6 (1.1) 298 (93.1%) 38 (11.9%)
0.0401 0.6148 0.4046 0.3762 0.1444 0.5096 0.0328 0.8004 0.3674 0.2929 0.4367 0.5222
Tender joint count, mean (SD) Swollen joint count, mean (SD) Chest expansion, mean (SD) Schober, mean (SD)
3.8 (1.6) 0.15 (0.85) 6.0 (4.9) 3.8 (1.6)
3.9 (1.7) 0.14 (0.90) 6.1 (4.3) 3.9 (1.7)
3.7 (1.5) 0.17 (0.81) 5.9 (5.3) 3.8 (1.6)
0.0465 0.6633 0.6883 0.0465
HLAB27+, n (%) CRP, mean (SD) Sacroiliac joint structural damage at plain X-Rays, n (%) Sacroiliitis at pelvic MRI, n (%) At least one syndesmophyte, n (%)
375 (59.0%) 8.3 (13.8) 308 (49.0%) 209 (33.4%) 151 (24.2%)
176 (55.7%) 6.6 (12.0) 150 (47.8%) 96 (31.1%) 67 (21.5)
199 (62.2%) 9.9 (15.3) 158 (50.3%) 113 (35.6%) 84 (26.8%)
0.0961 0.0034 0.5231 0.5231 0.1226
BMI: Body mass index; BASDAI: Bath ankylosing spondylitis disease activity index; BASFI: Bath ankylosing spondylitis functional index; HAQ: Health assessment questionnaire; SF36-MCS: Short form (36) mental component summary; SF36-PCS: Short form (36) physical component summary; BASMI: Bath ankylosing spondylitis metrology index; ASDAS: Ankylosing spondylitis disease activity score; CRP: C-reactive protein; NSAID: Non-steroidal anti-inflammatory drug; DMARD: Disease modifying antirheumatic drug.
• clinical data (e.g. body mass index, cervical spine rotation, intermalleolar distance, presence of thoracic pain); • biological data (C-reactive protein).
Improvement in BASFI was not associated with radiographic damage.
On average in the 5 samples imputed, the Hosmer-Lemeshow goodness-of-fit test showed a P value of 0.60 indicating that the model fitted the data well and the c-statistic was 0.79, asserting good discrimination. Graphs verifying the balance of characteristics at inclusion according to the exposure group are presented in Appendix A, Figs. S1 and S2; See the supplementary material associated with this article online. For the secondary analysis, the propensity model also included 16 variables.
3.5. Effect of physiotherapy on BASFI
3.4. Prognostic factors for improvement in BASFI Baseline characteristics associated with improvement in BASFI in our study sample were mostly those known to be pronostic factors for functional impairment in SpA [26,27], such as arthritis, C-reactive protein level or duration of axial symptoms (Table 2).
In all, 346 (52%) patients had an improvement of at least 20% in BASFI, 79 (47%) in the group with physiotherapy in the first 6 months and 268 (51%) in the group without physiotherapy. After adjusting for confounding factors, patients who had physiotherapy during the first 6 months had not more frequently an improvement of at least 20% in BASFI at 6 months (RR [IC95%]: 0.98 [0.82–1.17]). After using propensity score weighting, the results were similar (RR [IC95%]: 1.15 [0.91–1.45]) (Table 3). There were no improvement on BASFI at 1 and 2 years in the group with early physiotherapy compared to the group without physiotherapy (Table 4). Results were similar in sensitivity analyses after using a cut-off of 50% to define functional impairment (Table 3) and in analyses with others trimming cutpoints.
Table 3 Effect of physiotherapy on BASFI at 6 months. Improvement in BASFI > 20%
Unadjusted Adjusted for confounding factorsa Using PS weighting
Improvement in BASFI > 50%
No. of patients
RR (CI 95%)
P value
No. of patients
RR (CI 95%)
P value
689 689 689
0.96 (0.77; 1.18) 0.98 (0.82; 1.17) 1.15 (0.91–1.45)
0.67 0.82 0.24
689 689 689
0.88 (0.63; 1.22) 0.98 (0.76; 1.26) 1.20 (0.87–1.66)
0.44 0.90 0.27
a Confounding factors included: age, sex, physiotherapy (at least 8 sessions of physical therapy), BASFI, position change, SF36, intermalleolar distance, CRP and having radiographs in the 6 months before inclusion.
Please cite this article in press as: Escalas C, et al. Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.05.008
G Model
ARTICLE IN PRESS
BONSOI-4253; No. of Pages 6
C. Escalas et al. / Joint Bone Spine xxx (2015) xxx–xxx Table 4 Effect of early physiotherapy on secondary outcomes.
Improvement in BASFI > 20% at 6 months Improvement in BASFI > 20% at 1 year Improvement in BASFI > 20% at 2 years
No. of patients
RR (CI 95%)
P value
689
1.15 (0.91; 1.45)
0.24
671
0.94 (0.80; 1.11)
0.45
629
1.09 (0.90; 1.33)
0.36
After using propensity weighting, in patients who had regular physiotherapy in the first 2 years, the risk of improvement of at least 20% in BASFI did not differ compared to those who had not regular physiotherapy (RR [IC95%]: 0.90 [0.66–1.21]).
4. Discussion Supervised physiotherapy delivered in a primary care setting did not improve functional impairment in patients with early inflammatory back pain suggesting the diagnosis of SpA. Despite the recommendations [8,9], physiotherapy was prescribed in only 166 (24%) patients during the first 6 months and the percentages were similar in each period of 6 months during the 2-years followup. Thus during the whole follow-up period, the percentage of patients treated with physiotherapy remained broadly stable and low. However, patients who had physiotherapy received a high number of supervised sessions (23 sessions on average), which is not in accordance with the recommendation of limited number of supervised sessions followed by home-based exercises [13]. These observations suggest that the international recommendation concerning non-pharmacological treatments for SpA is not followed in France by a vast majority of rheumatologists. This trend was observed in the 25 centers who include patients suggesting that the absence of appropriation of the recommendation is homogenous in France and that there are no regional differences. Our results raise the question of whether physiotherapy is not efficient in real-life conditions, contradicting results of RCTs, or whether the absence of standardization of the physiotherapy programs and of physiotherapists skills for the treatment of SpA is the cause of the lack of efficacy on functional improvement. In fact, competencies and skills of physiotherapists working in a primary care setting in France in the management of patients with SpA are probably very heterogeneous and although SpA cannot be considered as a rare disease, physiotherapists in primary care setting mainly have to deal with the management of mechanical musculoskeletal conditions especially common low back pain. Dissemination through internet of standardized and individualized physical therapy programs for SpA for physiotherapists by association of professionals and/or patients is probably feasible with limited costs and deserves to be tested. As patients included in the cohort had short duration of symptoms and disease, the hypothesis of a lack of efficacy on functional improvement due to a floor effect with the BASDAI may appear relevant. Moreover, because of the low BASFI at inclusion, it was more difficult to demonstrate a significant variation in the followup. To our knowledge, there was no study reporting the use of physiotherapy in a primary care setting in patients with SpA and this study is one of the first to assess the effect of physiotherapy in a cohort. The use of propensity score in a cohort is becoming increasingly popular in situations where a randomized controlled trial is difficult or not feasible. Traditional methods of adjustment
5
are often limited since they can only use a limited number of covariates. However, propensity scores, which provide a scalar summary of the covariate information, do not have this limitation. Despite the large number of baseline variables available in the DESIR cohort, the possibility of unobserved confounding covariates was reduced but cannot be ruled out unlike in randomized trials. One of the major limitation of the study was the lack of adequation of the DESIR cohort to our analyses. The DESIR cohort was not designed to evaluate the effect of physiotherapy. Indeed, data about physiotherapy were incompletely collected, imprecise about the content of the sessions or the indication. Then the definition of the intervention was imprecise and the group of patients who received physiotherapy had finally a heterogeneous treatment. Moreover, there were also missing data on the reason for prescription of physiotherapy and we cannot exclude that a number of patients had physiotherapy for another reason than SpA. This absence of standardisation makes it difficult to strongly conclude about the effect of physiotherapy. In this first attempt to assess the efficacy of physiotherapy delivered in a primary care setting and in real-life conditions, we found no benefits on functional improvement for patients with early SpA. However, positive effects of physiotherapy for patients with SpA have been extensively demonstrated in several RCTs, pointing out the probable gap between physiotherapy programs delivered in daily practice and those delivered in RCTs. Dissemination of educational programs for caregivers, especially physiotherapists working in primary care, focusing on physical therapy for the management of patients with SpA deserves to be tested to improve functional limitations of these patients who do not always have access to specialized centers.
Disclosure of interest The authors declare that they have no competing interest.
Acknowledgments The DESIR cohort was sponsored by the Département de la Recherche Clinique et du Développement de l’Assistance Publique–Hôpitaux de Paris. This study is conducted under the umbrella of the French Society of Rheumatology and Institut National de la Santé et de la Recherche Médicale (INSERM). The database management is performed within the department of epidemiology and biostatistics (Pr Paul Landais, D.I.M., Nîmes, France). An unrestricted grant from Pfizer was allocated for the 10 years of the follow-up of the recruited patients. The authors thank the different regional participating centers: Pr Maxime Dougados (Paris - Cochin B), Pr André Kahan (Paris - Cochin A), Pr Olivier Meyer (Paris - Bichat), Pr Pierre Bourgeois (Paris - La Pitié Salpêtrière), Pr Francis Berenbaum (Paris - Saint Antoine), Pr Pascal Claudepierre (Créteil), Pr Maxime Breban (Boulogne Billancourt), Dr Bernadette Saint-Marcoux (Aulnay-sous-Bois), Pr Philippe Goupille (Tours), Pr Jean-Francis Maillefert (Dijon), Dr Xavier Puéchal, Dr Emmanuel Dernis (Le Mans), Pr Daniel Wendling (Besanc¸on), Pr Bernard Combe (Montpellier), Pr Liana Euller-Ziegler (Nice), Pr Philippe Orcel, Dr Pascal Richette (Paris - Lariboisière), Pr Pierre Lafforgue (Marseille), Dr Patrick Boumier (Amiens), Pr Jean-Michel Ristori, Pr Martin Soubrier (Clermont-Ferrand), Dr Nadia Mehsen (Bordeaux), Pr Damien Loeuille (Nancy), Pr René-Marc Flipo (Lille), Pr Alain Saraux (Brest), Pr Corinne Miceli (Le Kremlin Bicêtre), Pr Alain Cantagrel (Toulouse), Pr Olivier Vittecoq (Rouen). The authors also thank URC-CIC Paris Centre for the coordination and monitoring of the study.
Please cite this article in press as: Escalas C, et al. Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.05.008
G Model BONSOI-4253; No. of Pages 6
ARTICLE IN PRESS C. Escalas et al. / Joint Bone Spine xxx (2015) xxx–xxx
6
Appendix A. Supplementary data Supplementary data (Figs. S1-S2) associated with this article can be found in the online version at http://dx.doi.org/10.1016/ j.jbspin.2015.05.008.
[13] [14]
References [15] [1] Sieper J, Braun J, Rudwaleit M, et al. Ankylosing spondylitis: an overview. Ann Rheum Dis 2002;61:8–18. [2] Khan MA. Update on spondyloarthropathies. Ann Intern Med 2002;136:896–907. [3] Giannotti E, Trainito S, Arioli G, et al. Effects of physical therapy for the management of patients with ankylosing spondylitis in the biological era. Clin Rheumatol 2014;33:1217–30. [4] Masiero S, Bonaldo L, Pigatto M, et al. Rehabilitation treatment in patients with ankylosing spondylitis stabilized with tumor necrosis factor inhibitor therapy: a randomized controlled trial. J Rheumatol 2011;38:1335–42. [5] Masiero S, Poli P, Bonaldo L, et al. Supervised training and home-based rehabilitation in patients with stabilized ankylosing spondylitis on TNF inhibitor treatment: a controlled clinical trial with a 12-month follow-up. Clin Rehabil 2013;28:562–72. [6] Kjeken I, Bø I, Rønningen A, et al. A three-week multidisciplinary in-patient rehabilitation programme had positive long-term effects in patients with ankylosing spondylitis: randomized controlled trial. J Rehabil Med 2013;45:260–7. [7] Ciprian L, Lo Nigro A, Rizzo M, et al. The effects of combined spa therapy and rehabilitation on patients with ankylosing spondylitis being treated with TNF inhibitors. Rheumatol Int 2013;33:241–5. [8] Zochling J, van der Heijde D, Burgos-Vargas R, et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2006;65:442–52. [9] Wendling D, Lukas C, Paccou J, et al. Recommendations of the French Society of Rheumatology (SFR) on the everyday management of patients with spondyloarthritis. Joint Bone Spine 2014;81:6–14. [10] Ozgocmen S, Akgul O, Altay Z, et al. Expert opinion and key recommendations for the physical therapy and rehabilitation of patients with ankylosing spondylitis. Int J Rheum Dis 2012;15:229–38. [11] Zochling J, van der Heijde D, Dougados M, et al. Current evidence for the management of ankylosing spondylitis: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Ann Rheum Dis 2006;65:423–32. [12] Van den Berg R, Baraliakos X, Braun J, et al. First update of current evidence for the management of ankylosing sponddylitis with non-pharmacological
[16] [17] [18]
[19]
[20] [21]
[22]
[23] [24] [25]
[26] [27]
treatment and non-biologic drugs: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Rheumatology 2012;51:1388–96. Dagfinrud H, Kvien TK, Hagen KB. Physiotherapy interventions for ankylosing spondylitis. Cochrane Database Syst Rev 2008;23:CD002822. Dougados M, d’Agostino MA, Benessiano J, et al. The DESIR cohort: a 10year follow-up of early inflammatory back pain in France: study design and baseline characteristics of the 708 recruited patients. Joint Bone Spine 2011;78:598–603. Claudepierre P. Spondyloarthritis: a window of opportunity? Joint Bone Spine 2014;81:197–9. Wendling D, Claudepierre P, Prati C. Early diagnosis and management are crucial in spondyloarthritis. Joint Bone Spine 2013;80:582–5. Calin A, Porta J, Fries JF, et al. Clinical history as a screening test for ankylosing spondylitis. JAMA 1977;237:2613–4. Rudwaleit M, Metter A, Listing J, et al. Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria. Arthritis Rheum 2006;54:569–78. Swinkels IC, Wimmers RH, Groenewegen PP, et al. What factors explain the number of physical therapy treatment sessions in patients referred with low back pain: a multilevel analysis. BMC Health Serv Res 2005;24: 74. Calin A. Can we define the outcome ok ankylosing spondylitis and the effect of physiotherapy management? J Rheumatol 1994;21:184–5. Tubach F, Ravaud P, Martin-Mola E, et al. Minimum Clinically important improvement and patient acceptable symptom state in pain and function in rheumatoid arthritis, ankylosing spondylitis, chronic back pain, hand osteoarthritis, and hip and knee osteoarthritis: results from a prospective multinational study. Arthritis Care Res 2012;64:1699–707. Anderson JJ, Baron G, van der Heijde D, et al. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum 2001;44:1876–86. Rosenbaum PR. The central role of the propensity score in observational studies for causal effects. Biometrika 1983;70:41–55. Austin PC. The performance of different propensity score methods for estimating marginal hazard ratios. Stat Med 2013;32:2837–49. Harder VS, Stuart EA, Anthony JC. Propensity score techniques and the assessment of measured covariate balance to test causal associations in psychological research. Psychol Methods 2010;15:234–49. Doran MF, Brophy S, Mackay K, et al. Predictors of longterm outcome in ankylosing spondylitis. J Rheumatol 2003;30:316–20. Cansu DU, Calisir C, Savas Yasas U, et al. Predictors severity and functional disability in Turkish patients with ankylosing spondylitis. Clin Rheumatol 2011;30:557–62.
Please cite this article in press as: Escalas C, et al. Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.05.008
ARTICLE IN PRESS Joint Bone Spine xxx (2015) xxx–xxx
Available online at
ScienceDirect www.sciencedirect.com
Original article
Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort Cécile Escalas a , Marie Dalichampt b , Maxime Dougados c , Serge Poiraudeau a,∗,b a Department of Physical Medicine and Rehabilitation, AP–HP, Paris Descartes University, Cochin Hospital, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France b Inserm U1153 and IFR Handicap, Cochin Hospital, 75014 Paris, France c Inserm U1153, Clinical epidemiology and biostatistics, Department of Rheumatology, Cochin Hospital, AP–HP, Paris Descartes University, PRES Sorbonne Paris-Cité, 75014 Paris, France
a r t i c l e
i n f o
Article history: Accepted 7 May 2015 Available online xxx Keywords: Axial spondyloarthritis Physical therapy Treatment and epidemiology
a b s t r a c t Objective: To evaluate the effect of physiotherapy on functional limitation in an observational cohort of early axial spondyloarthritis. Methods: Design: prospective population-based cohort study. Patients: 708 patients with early axial spondyloarthritis between 2007 and 2010 naive of TNF blockers. Intervention: early physiotherapy defined by at least eight supervised sessions of physical therapy during the first six months. Measurements: the primary outcome was functional improvement defined by a relative improvement of at least 20% in BASFI at six months. Secondary outcomes were improvement in BASFI at one and two years and ASAS20 response criteria at six months. Statistical analysis: a propensity score of having physiotherapy was developed and multivariate analysis using propensity score weighting were used to assess the effect of physiotherapy on outcome. Results: Overall, 166 (24%) patients had physiotherapy during the first six months. After using propensity score weighting, there was no functional improvement on the primary outcome in patients treated with early physical therapy (relative risk [IC95%]: 1.15 [0.91–1.45]). No differences were observed on secondary outcomes (relative risk [IC95%]: 0.94 [0.80–1.11]). Conclusions: It seems there is no functional benefit for patients with early spondyloarthritis to be treated early by physiotherapy in daily practice, even though the efficacy of physiotherapy has been shown in several randomized controlled studies. © 2015 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
1. Introduction Axial spondyloarthritis (SpA) is a chronic inflammatory rheumatic disease most commonly affecting the axial skeleton, which historically has been difficult to treat. SpA starts commonly early in life and can lead to severe damage of spine with functional impairment, disability and poor quality of life [1,2]. Physical therapy seems to play an important role in the management of patients with SpA. The primary aim of exercise treatment is to avoid stiffening in a flexed position and to improve functional capacity and quality of life. Several randomized controlled trials have demonstrated that physical therapy with various modalities has positive effects on pain and function in SpA [3–7]. The recent recommendations emphasize that non-pharmacological treatment
∗ Corresponding author. E-mail address: [email protected] (S. Poiraudeau).
of SpA should include regular exercise and that individual and group physical therapy sessions should be considered [8,9]. Physiotherapy should be started as soon as SpA is diagnosed and lifelong regular exercises are the mainstay of the treatment [10]. A combined regime of inpatient spa-exercise therapy followed by group physiotherapy is recommended for the highest benefit, and group physiotherapy is also superior to home exercise; the conventional protocols of physiotherapy, including flexibility, stretching and breathing exercises, as well as pool and land-based exercises are recommended. The review by Zochling et al. [11] and a recent systematic review [12] showed that exercises have positive effects on BASFI, BASDAI, pain and mobility function. A Cochrane review on the role of physiotherapy interventions in SpA also concluded that physical therapy (physiotherapy, home exercises, spa therapy) is beneficial [13]. However, small numbers of participants in many trials, heterogeneity of the interventions and outcomes measures and deficiency in reporting data result in wide intervals and lack of strong
http://dx.doi.org/10.1016/j.jbspin.2015.05.008 1297-319X/© 2015 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Escalas C, et al. Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.05.008
G Model BONSOI-4253; No. of Pages 6
ARTICLE IN PRESS C. Escalas et al. / Joint Bone Spine xxx (2015) xxx–xxx
2
evidence. Moreover, it is not clear which treatment protocol and when during the evolution of the disease should be recommended. Finally, no study reporting the effectiveness of physical therapy for SpA in real-life conditions have been published and there could be a substantial gap between physical therapy performed in randomized controlled trials and in daily practice. Moreover, all trials have been conducted in patients who fulfilled New York modified criteria, i.e. who had structural damage of the sacroiliac, and in an advanced stage of their disease. But to our knowledge, no study has reported the effect of physiotherapy in patients with early SpA or without radiographic damage. However, some data suggest that management in early stage of the disease could be decisive [14,15]. “Devenir des Spondylarthropathies Indifférenciées Récentes” (DESIR) is a prospective longitudinal cohort involving 25 rheumatology centres and 708 patients with recent (≤ 3 years) inflammatory back pain suggesting a diagnosis of SpA [16]. These patients can receive any treatment in accordance with their rheumatologist’s decision. Therefore, this cohort represents a unique opportunity to evaluate the current practice and the effect of physiotherapy in real-life conditions. Our main objective was to assess whether physiotherapy delivered in a primary care setting improves function in patients with early inflammatory back pain suggesting a diagnosis of SpA. 2. Methods 2.1. Patients A total of 708 patients with early inflammatory back pain have been included in the DESIR cohort between October 2007 and April 2010 in 25 regional centres in France, with visits scheduled every 6 months during 2 years [16]. Consecutive patients aged > 18 years and < 50 years with inflammatory back pain for more than 3 months and less than 3 years and symptoms suggestive of SpA according to the rheumatologists’ assessment were included in the DESIR cohort. Patients had to fulfil either the Calin or Berlin criteria [17,18]. Patients with a definite diagnosis of non-SpA back pain, conditions that might interfere with the validity of the informed consent and/or prevent an optimal compliance (e.g., alcoholism, psychiatric disorders) and a history of TNF␣ blocker usage were excluded. 2.2. Intervention At each visit in the DESIR cohort, patients reported the number of sessions and the reason for physical therapy. The number of sessions for each patient per 6 months was used to compare patients who had or had not physical therapy. Early physiotherapy was defined as at least 8 supervised sessions of physical therapy in the first 6 months. The optimal number of sessions is unknown and seems to vary between 6 and 10 according to the studies in rheumatic disease. The number of 8 treatment sessions was chosen because this is the number usually accepted to be efficient in daily practice and it corresponds to the number of sessions in studies reporting effect of physiotherapy [19]. Regular physiotherapy was defined as at least 8 supervised sessions of physical therapy in at least 3 periods of 6 months during the first 24 months. 2.3. Measurements The primary outcome measure was an improvement in the patient functional limitation. The Bath Ankylosing Spondylitis Functional Index (BASFI) is a validated self-assessment tool that determines the degree of functional limitation in SpA patient using a 100 mm visual analog scale measuring level of ability with activities in the last 48 h [20]. Functional improvement was defined as a
relative improvement of at least 20% in BASFI, which corresponds to the definition of minimum clinically important improvement in function in rheumatic disease [21] and with the 20% improvement response according to the criteria of the Assessment in Ankylosing Spondylitis (ASAS) International Working Group (ASAS 20 responders) usually used in SpA [22]. Functional improvement was evaluated at 6 months. Secondary endpoints were improvement in BASFI at one and two years. 2.4. Statistical analysis 2.4.1. Descriptive analysis The percentage of patients having physiotherapy and its 95% confidence interval and the number of sessions were evaluated at each intermediate follow-up visit (e.g. 6, 12, 18 and 24 months). Baseline characteristics of patients were compared: qualitative variables were compared with the Chi2 test (Fischer’s exact test when appropriate) and quantitative variables with one-way analysis of variance (ANOVA) (Mann-Whitney U-test when appropriate). 2.4.2. Effect of physiotherapy The effect of early physiotherapy was evaluated as follows. Study outcomes were estimated as part of a linear model using generalized estimating equations. A binomial distribution and log-link function were chosen for the binary criteria to assess relative risks in the context of frequent outcomes. When a convergence problem occurred, a Poisson distribution was used. The variance-covariance matrix was postulated by a symmetrical composition so a constant correlation between two patients in the same hospital could be considered. A Markov chain Monte Carlo method of multiple imputations was used to impute missing data. Five samples imputed were used and variables with more than 20% of missing data were excluded. To take into account the bias in treatment assignment in observational studies, a propensity score method was applied [23]. Formally, the propensity score is the probability of receiving a particular treatment conditional on the individual’s covariate values at baseline. Expecting differences between patients who had or had not physical therapy, a propensity score was used as the probability that a patient with specific baseline characteristics would have physical therapy. Potential confounders at baseline, including all demographic, clinical, radiological and biological data, were selected with automatic stepwise selection procedure in a logistic regression model for each imputed sample to construct the final propensity score model. The propensity score model calibration (Hosmer-Lemeshow goodness-of-fit test) and discrimination performance (area under the receiver operating curve) were evaluated on each imputed sample. A standardized mortality ratio propensity score weight was then used. Patients in the physical therapy group received a weight of 1 and those in the non physical therapy group received a weight of pi/(1−pi) where pi refers to an individual’s probability of having early physiotherapy. Using these weights allowed to estimate the average treatment effect in the treated group (ATT) [24]. The propensity score weights were then incorporated as weights into a generalized linear model with only the physical therapy group as a predictor variable and no covariate. Biases from extreme weights were adjusted by using trimming technique that trims the stabilized weights within a specific range [25]. The balance in baseline risks factors was evaluated in the original and the weighted population by computing the standardized differences. The adequate balance was considered achieved for standardized difference < 10%. At the end, relative risks were estimated with 3 models: the crude model, a classical covariate-adjusted generalized linear model and the propensity model. For each model, the significance level was set at 5%. For propensity analysis, trimming cutpoint with the best balance properties was chosen as main analysis and analyses with
Please cite this article in press as: Escalas C, et al. Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.05.008
G Model BONSOI-4253; No. of Pages 6
ARTICLE IN PRESS C. Escalas et al. / Joint Bone Spine xxx (2015) xxx–xxx
3
Table 1 Baseline patient characteristics according to physiotherapy status in the first 6 months. All patients (N = 689)
Patients without physiotherapy in the first 6 months (N = 523)
Patients with physiotherapy in the first 6 months (N = 166)
P
Age, mean (SD), year Female gender, n (%) Graduate studies, n (%) Missing workdays, median (IQR) BMI, mean (SD), kg/m2
33.3 (8.6) 371 (53.8%) 409 (59.7%) 5 [0–30] 23.9 (4.1)
33.0 (8.8) 258 (49.3%) 308 (59.3%) 3.5 [0–21] 24.1 (4.1)
34.5 (8.0) 113 (68.1%) 101 (60.8%) 10 [0–50] 23.4 (3.8)
0.0486 < 0.0001 0.7319 0.0007 0.0434
Duration of axial symptoms, mean (SD), month Intensity of axial pain, mean (SD) Peripheric joint involvement, n (%) Current clinical manifestations Thoracic pain, n (%) Lumbar pain, n (%) Buttock pain, n (%) BASDAI, mean (SD) BASMI, mean (SD) BASFI, mean (SD) HAQ, mean (SD) SF 36–MCS, mean (SD) SF 36–PCS, mean (SD) ASQol, median (IQR) ASDAS, mean (SD) NSAID intake, n (%) DMARD intake, n (%)
18.5 (10.6) 5.0 (2.7) 395 (57.3%)
18.6 (10.6) 4.8 (2.7) 292 (55.8%)
18.1 (10.9) 5.5 (2.5) 103 (62.0%)
0.5644 0.0042 0.1583
393 (57.0%) 623 (90.4%) 511 (74.2%) 44.9 (20.0) 2.4 (1.0) 30.6 (22.9) 0.67 (0.52) 40.1 (11.2) 39.9 (9.3) 10.0 [5.0–14.0] 2.5 (1.0) 636 (92.3%) 89 (12.9%)
273 (52.2%) 467 (89.3%) 380 (72.7%) 43.4 (20.3) 2.3 (1.0) 29.7 (23.2) 0.64 (0.52) 40.9 (11.3) 40.9 (9.3) 9.0 [5.0–13.0] 2.5 (1.0) 482 (92.2%) 69 (13.2%)
120 (72.3%) 156 (94.0%) 131 (78.9%) 49.7 (18.4) 2.6 (1.1) 33.7 (21.7) 0.79 (0.51) 37.8 (10.9) 37.0 (8.6) 11.5 [8.0–15.0] 2.6 (1.0) 154 (92.8%) 20 (12.0%)
< 0.0001 0.0740 0.1085 0.0004 0.0032 0.0507 0.0012 0.0026 < 0.0001 0.0001 0.1023 0.7971 0.7016
Tender joint count, mean (SD) Swollen joint count, mean (SD) Chest expansion, mean (SD) Schober, mean (SD)
4.3 (8.6) 0.15 (0.83) 6.0 (4.7) 3.8 (1.6)
3.8 (8.0) 0.12 (0.71) 6.1 (5.3) 3.8 (1.6)
5.8 (10.1) 0.22 (1.12) 5.6 (2.0) 3.6 (1.7)
0.0100 0.1816 0.1741 0.1228
HLAB27+, n (%) CRP, mean (SD) Sacroiliac joint structural damage at plain X-Rays, n (%) Sacroiliitis at pelvic MRI, n (%)
400 (58.1%) 8.1 (13.6) 336 (49.5%)
311 (59.6%) 8.1 (12.6) 71 (43.8%)
89 (53.6%) 8.2 (16.4) 265 (51.3%)
0.1749 0.9095 0.0988
228 (33.9%)
48 (29.6%)
180 (35.2%)
0.1898
BMI: Body mass index; BASDAI: Bath ankylosing spondylitis disease activity index; BASMI: Bath ankylosing spondylitis metrology index; BASFI: Bath ankylosing spondylitis functional index; HAQ: Health assessment questionnaire; SF36-MCS: Short form (36) mental component summary; SF36-PCS: Short form (36) physical component summary; ASQol: Ankylosing spondylitis quality of life; ASDAS: Ankylosing spondylitis disease activity score; NSAID: Non-steroidal anti-inflammatory drug; DMARD: Disease modifying anti-rheumatic drug; CRP: C-reactive protein.
others trimming cutpoints were presented as sensitivity analyses. Others sensitivity analyses were conducted using a cut off of 50% to define improvement of functional limitation. Finally, a secondary analysis was performed with the same methodology to estimate the effect of regular physiotherapy (at least 8 supervised sessions of physical therapy in at least 3 periods of 6 months during the first 24 months) on functional improvement (relative improvement of at least 20% in BASFI) at 2 years. Statistical analysis was carried out with SAS software, version 9-1 (SAS Institute Inc., Cary, NC, USA). 3. Results 3.1. Characteristics of the population In total, 689 patients were analysed. Baseline characteristics of the population and comparison between patients who had or had not physiotherapy in the first 6 months are presented in Table 1. At inclusion, 514 (74.6%) patients fulfilled the ASAS criteria for axial SpA. According to inclusion criteria in the DESIR cohort, this population was characterised by young age (mean age 33.3 ± 8.6 years) and short duration of axial symptoms (mean 18.5 ± 10.6 months); 53.8% were women. Patients had high disease activity with a mean BASDAI of 44.9 (± 20.0) and a mean CRP of 8.1 (± 13.6). The mean BASFI was 30.6 (± 22.9) and the mean HAQ was 0.67 (± 0.52). HLAB27 was positive in 58.1% of the patients, 49.5% had sacroiliac joint structural damage at plain X-Rays and 33.9% sacroiliitis at pelvic MRI. Characteristics between patients who had or had not physiotherapy in the first 6 months were generally
comparable, except for sex, intensity of axial pain, presence of thoracic pain, BASDAI and quality of life index. Patients with physiotherapy tended to be more frequently women, to have more sick leaves, to have a higher level of disease activity and a worse quality of life.
3.2. Frequency of physiotherapy In all, 166 (24%) patients had physiotherapy during the first 6 months. The percentage of patients with physiotherapy during each period of 6 months decreased slowly, respectively 22%; 18% and 18% between 6 months and 12 months; 12 months and 18 months and 18 months and 24 months. Between inclusion and 6 months, the mean number of sessions of physiotherapy in the whole group was 7.4 (± 13.2) and the mean number of sessions in patients with physiotherapy was 23.1 (± 14.2). Among the 661 patients who went to at least 3 follow-up visits in the first 2 years, 271 (41%) had at least one period of 6 months with 8 sessions of physiotherapy and 88 (13%) had regular physiotherapy (8 sessions in at least 3 periods of 6 months in the first 2 years).
3.3. Propensity models The most accurate propensity model included 16 variables, including: • demographics data (e.g. sex, change of job, sick leaves);
Please cite this article in press as: Escalas C, et al. Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.05.008
G Model
ARTICLE IN PRESS
BONSOI-4253; No. of Pages 6
C. Escalas et al. / Joint Bone Spine xxx (2015) xxx–xxx
4 Table 2 Prognostic factors for improvement in BASFI at 6 months.
All patients (N = 637)
Patients without improvement in BASFI (N = 317)
Patients with improvement in BASFI (N = 320)
P
Age, mean (SD), year Female gender, n (%) Graduate studies, n (%) Disability status, n (%) Tobacco use, n (%) Alcohol excess, n (%) BMI, mean (SD), kg/m2
33.4 (8.6) 347 (54.5%) 387 (60.9%) 26 (4.1%) 223 (35.2%) 94 (14.9%) 23.9 (4.1)
33.8 (8.6) 190 (59.9%) 180 (57.1%) 20 (6.3) 121 (38.3%) 45 (14.3%) 24.1 (4.2)
32.9 (8.7) 157 (49.1%) 207 (64.7%) 6 (1.9) 102 (32.2) 49 (15.5%) 23.7 (3.9)
0.2294 < 0.0059 0.0514 0.0047 0.1073 0.6668 0.1939
Duration of axial symptoms, mean (SD), month Peripheric joint involvement, n (%) Intensity of axial pain, mean (SD) BASDAI, mean (SD) BASFI, mean (SD) HAQ, mean (SD) SF 36-MCS, mean (SD) SF 36-PCS, mean (SD) BASMI, mean (SD) ASDAS, mean (SD) NSAID intake, n (%) DMARD intake, n (%)
18.6 (10.6) 364 (57.1%) 4.9 (2.7) 44.8 (20.1) 30.3 (22.8) 0.67 (0.52) 40.2 (11.3) 40.0 (9.4) 2.4 (1.0) 2.5 (1.0) 588 (92.3%) 81 (12.7%)
19.5 (10.5) 178 (56.2%) 5.0 (2.7) 45.5 (20.5) 29.0 (22.6) 0.68 (0.52) 39.2 (11.1) 39.9 (9.1) 2.4 (1.0) 2.5 (1.0) 290 (91.5%) 43 (13.6%)
17.7 (10.7) 186 (58.1%) 4.9 (2.7) 44.1 (19.6) 31.7 (22.9) 0.65 (0.52) 41.2 (11.5) 40.1 (9.6) 2.4 (1.0) 2.6 (1.1) 298 (93.1%) 38 (11.9%)
0.0401 0.6148 0.4046 0.3762 0.1444 0.5096 0.0328 0.8004 0.3674 0.2929 0.4367 0.5222
Tender joint count, mean (SD) Swollen joint count, mean (SD) Chest expansion, mean (SD) Schober, mean (SD)
3.8 (1.6) 0.15 (0.85) 6.0 (4.9) 3.8 (1.6)
3.9 (1.7) 0.14 (0.90) 6.1 (4.3) 3.9 (1.7)
3.7 (1.5) 0.17 (0.81) 5.9 (5.3) 3.8 (1.6)
0.0465 0.6633 0.6883 0.0465
HLAB27+, n (%) CRP, mean (SD) Sacroiliac joint structural damage at plain X-Rays, n (%) Sacroiliitis at pelvic MRI, n (%) At least one syndesmophyte, n (%)
375 (59.0%) 8.3 (13.8) 308 (49.0%) 209 (33.4%) 151 (24.2%)
176 (55.7%) 6.6 (12.0) 150 (47.8%) 96 (31.1%) 67 (21.5)
199 (62.2%) 9.9 (15.3) 158 (50.3%) 113 (35.6%) 84 (26.8%)
0.0961 0.0034 0.5231 0.5231 0.1226
BMI: Body mass index; BASDAI: Bath ankylosing spondylitis disease activity index; BASFI: Bath ankylosing spondylitis functional index; HAQ: Health assessment questionnaire; SF36-MCS: Short form (36) mental component summary; SF36-PCS: Short form (36) physical component summary; BASMI: Bath ankylosing spondylitis metrology index; ASDAS: Ankylosing spondylitis disease activity score; CRP: C-reactive protein; NSAID: Non-steroidal anti-inflammatory drug; DMARD: Disease modifying antirheumatic drug.
• clinical data (e.g. body mass index, cervical spine rotation, intermalleolar distance, presence of thoracic pain); • biological data (C-reactive protein).
Improvement in BASFI was not associated with radiographic damage.
On average in the 5 samples imputed, the Hosmer-Lemeshow goodness-of-fit test showed a P value of 0.60 indicating that the model fitted the data well and the c-statistic was 0.79, asserting good discrimination. Graphs verifying the balance of characteristics at inclusion according to the exposure group are presented in Appendix A, Figs. S1 and S2; See the supplementary material associated with this article online. For the secondary analysis, the propensity model also included 16 variables.
3.5. Effect of physiotherapy on BASFI
3.4. Prognostic factors for improvement in BASFI Baseline characteristics associated with improvement in BASFI in our study sample were mostly those known to be pronostic factors for functional impairment in SpA [26,27], such as arthritis, C-reactive protein level or duration of axial symptoms (Table 2).
In all, 346 (52%) patients had an improvement of at least 20% in BASFI, 79 (47%) in the group with physiotherapy in the first 6 months and 268 (51%) in the group without physiotherapy. After adjusting for confounding factors, patients who had physiotherapy during the first 6 months had not more frequently an improvement of at least 20% in BASFI at 6 months (RR [IC95%]: 0.98 [0.82–1.17]). After using propensity score weighting, the results were similar (RR [IC95%]: 1.15 [0.91–1.45]) (Table 3). There were no improvement on BASFI at 1 and 2 years in the group with early physiotherapy compared to the group without physiotherapy (Table 4). Results were similar in sensitivity analyses after using a cut-off of 50% to define functional impairment (Table 3) and in analyses with others trimming cutpoints.
Table 3 Effect of physiotherapy on BASFI at 6 months. Improvement in BASFI > 20%
Unadjusted Adjusted for confounding factorsa Using PS weighting
Improvement in BASFI > 50%
No. of patients
RR (CI 95%)
P value
No. of patients
RR (CI 95%)
P value
689 689 689
0.96 (0.77; 1.18) 0.98 (0.82; 1.17) 1.15 (0.91–1.45)
0.67 0.82 0.24
689 689 689
0.88 (0.63; 1.22) 0.98 (0.76; 1.26) 1.20 (0.87–1.66)
0.44 0.90 0.27
a Confounding factors included: age, sex, physiotherapy (at least 8 sessions of physical therapy), BASFI, position change, SF36, intermalleolar distance, CRP and having radiographs in the 6 months before inclusion.
Please cite this article in press as: Escalas C, et al. Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.05.008
G Model
ARTICLE IN PRESS
BONSOI-4253; No. of Pages 6
C. Escalas et al. / Joint Bone Spine xxx (2015) xxx–xxx Table 4 Effect of early physiotherapy on secondary outcomes.
Improvement in BASFI > 20% at 6 months Improvement in BASFI > 20% at 1 year Improvement in BASFI > 20% at 2 years
No. of patients
RR (CI 95%)
P value
689
1.15 (0.91; 1.45)
0.24
671
0.94 (0.80; 1.11)
0.45
629
1.09 (0.90; 1.33)
0.36
After using propensity weighting, in patients who had regular physiotherapy in the first 2 years, the risk of improvement of at least 20% in BASFI did not differ compared to those who had not regular physiotherapy (RR [IC95%]: 0.90 [0.66–1.21]).
4. Discussion Supervised physiotherapy delivered in a primary care setting did not improve functional impairment in patients with early inflammatory back pain suggesting the diagnosis of SpA. Despite the recommendations [8,9], physiotherapy was prescribed in only 166 (24%) patients during the first 6 months and the percentages were similar in each period of 6 months during the 2-years followup. Thus during the whole follow-up period, the percentage of patients treated with physiotherapy remained broadly stable and low. However, patients who had physiotherapy received a high number of supervised sessions (23 sessions on average), which is not in accordance with the recommendation of limited number of supervised sessions followed by home-based exercises [13]. These observations suggest that the international recommendation concerning non-pharmacological treatments for SpA is not followed in France by a vast majority of rheumatologists. This trend was observed in the 25 centers who include patients suggesting that the absence of appropriation of the recommendation is homogenous in France and that there are no regional differences. Our results raise the question of whether physiotherapy is not efficient in real-life conditions, contradicting results of RCTs, or whether the absence of standardization of the physiotherapy programs and of physiotherapists skills for the treatment of SpA is the cause of the lack of efficacy on functional improvement. In fact, competencies and skills of physiotherapists working in a primary care setting in France in the management of patients with SpA are probably very heterogeneous and although SpA cannot be considered as a rare disease, physiotherapists in primary care setting mainly have to deal with the management of mechanical musculoskeletal conditions especially common low back pain. Dissemination through internet of standardized and individualized physical therapy programs for SpA for physiotherapists by association of professionals and/or patients is probably feasible with limited costs and deserves to be tested. As patients included in the cohort had short duration of symptoms and disease, the hypothesis of a lack of efficacy on functional improvement due to a floor effect with the BASDAI may appear relevant. Moreover, because of the low BASFI at inclusion, it was more difficult to demonstrate a significant variation in the followup. To our knowledge, there was no study reporting the use of physiotherapy in a primary care setting in patients with SpA and this study is one of the first to assess the effect of physiotherapy in a cohort. The use of propensity score in a cohort is becoming increasingly popular in situations where a randomized controlled trial is difficult or not feasible. Traditional methods of adjustment
5
are often limited since they can only use a limited number of covariates. However, propensity scores, which provide a scalar summary of the covariate information, do not have this limitation. Despite the large number of baseline variables available in the DESIR cohort, the possibility of unobserved confounding covariates was reduced but cannot be ruled out unlike in randomized trials. One of the major limitation of the study was the lack of adequation of the DESIR cohort to our analyses. The DESIR cohort was not designed to evaluate the effect of physiotherapy. Indeed, data about physiotherapy were incompletely collected, imprecise about the content of the sessions or the indication. Then the definition of the intervention was imprecise and the group of patients who received physiotherapy had finally a heterogeneous treatment. Moreover, there were also missing data on the reason for prescription of physiotherapy and we cannot exclude that a number of patients had physiotherapy for another reason than SpA. This absence of standardisation makes it difficult to strongly conclude about the effect of physiotherapy. In this first attempt to assess the efficacy of physiotherapy delivered in a primary care setting and in real-life conditions, we found no benefits on functional improvement for patients with early SpA. However, positive effects of physiotherapy for patients with SpA have been extensively demonstrated in several RCTs, pointing out the probable gap between physiotherapy programs delivered in daily practice and those delivered in RCTs. Dissemination of educational programs for caregivers, especially physiotherapists working in primary care, focusing on physical therapy for the management of patients with SpA deserves to be tested to improve functional limitations of these patients who do not always have access to specialized centers.
Disclosure of interest The authors declare that they have no competing interest.
Acknowledgments The DESIR cohort was sponsored by the Département de la Recherche Clinique et du Développement de l’Assistance Publique–Hôpitaux de Paris. This study is conducted under the umbrella of the French Society of Rheumatology and Institut National de la Santé et de la Recherche Médicale (INSERM). The database management is performed within the department of epidemiology and biostatistics (Pr Paul Landais, D.I.M., Nîmes, France). An unrestricted grant from Pfizer was allocated for the 10 years of the follow-up of the recruited patients. The authors thank the different regional participating centers: Pr Maxime Dougados (Paris - Cochin B), Pr André Kahan (Paris - Cochin A), Pr Olivier Meyer (Paris - Bichat), Pr Pierre Bourgeois (Paris - La Pitié Salpêtrière), Pr Francis Berenbaum (Paris - Saint Antoine), Pr Pascal Claudepierre (Créteil), Pr Maxime Breban (Boulogne Billancourt), Dr Bernadette Saint-Marcoux (Aulnay-sous-Bois), Pr Philippe Goupille (Tours), Pr Jean-Francis Maillefert (Dijon), Dr Xavier Puéchal, Dr Emmanuel Dernis (Le Mans), Pr Daniel Wendling (Besanc¸on), Pr Bernard Combe (Montpellier), Pr Liana Euller-Ziegler (Nice), Pr Philippe Orcel, Dr Pascal Richette (Paris - Lariboisière), Pr Pierre Lafforgue (Marseille), Dr Patrick Boumier (Amiens), Pr Jean-Michel Ristori, Pr Martin Soubrier (Clermont-Ferrand), Dr Nadia Mehsen (Bordeaux), Pr Damien Loeuille (Nancy), Pr René-Marc Flipo (Lille), Pr Alain Saraux (Brest), Pr Corinne Miceli (Le Kremlin Bicêtre), Pr Alain Cantagrel (Toulouse), Pr Olivier Vittecoq (Rouen). The authors also thank URC-CIC Paris Centre for the coordination and monitoring of the study.
Please cite this article in press as: Escalas C, et al. Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.05.008
G Model BONSOI-4253; No. of Pages 6
ARTICLE IN PRESS C. Escalas et al. / Joint Bone Spine xxx (2015) xxx–xxx
6
Appendix A. Supplementary data Supplementary data (Figs. S1-S2) associated with this article can be found in the online version at http://dx.doi.org/10.1016/ j.jbspin.2015.05.008.
[13] [14]
References [15] [1] Sieper J, Braun J, Rudwaleit M, et al. Ankylosing spondylitis: an overview. Ann Rheum Dis 2002;61:8–18. [2] Khan MA. Update on spondyloarthropathies. Ann Intern Med 2002;136:896–907. [3] Giannotti E, Trainito S, Arioli G, et al. Effects of physical therapy for the management of patients with ankylosing spondylitis in the biological era. Clin Rheumatol 2014;33:1217–30. [4] Masiero S, Bonaldo L, Pigatto M, et al. Rehabilitation treatment in patients with ankylosing spondylitis stabilized with tumor necrosis factor inhibitor therapy: a randomized controlled trial. J Rheumatol 2011;38:1335–42. [5] Masiero S, Poli P, Bonaldo L, et al. Supervised training and home-based rehabilitation in patients with stabilized ankylosing spondylitis on TNF inhibitor treatment: a controlled clinical trial with a 12-month follow-up. Clin Rehabil 2013;28:562–72. [6] Kjeken I, Bø I, Rønningen A, et al. A three-week multidisciplinary in-patient rehabilitation programme had positive long-term effects in patients with ankylosing spondylitis: randomized controlled trial. J Rehabil Med 2013;45:260–7. [7] Ciprian L, Lo Nigro A, Rizzo M, et al. The effects of combined spa therapy and rehabilitation on patients with ankylosing spondylitis being treated with TNF inhibitors. Rheumatol Int 2013;33:241–5. [8] Zochling J, van der Heijde D, Burgos-Vargas R, et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2006;65:442–52. [9] Wendling D, Lukas C, Paccou J, et al. Recommendations of the French Society of Rheumatology (SFR) on the everyday management of patients with spondyloarthritis. Joint Bone Spine 2014;81:6–14. [10] Ozgocmen S, Akgul O, Altay Z, et al. Expert opinion and key recommendations for the physical therapy and rehabilitation of patients with ankylosing spondylitis. Int J Rheum Dis 2012;15:229–38. [11] Zochling J, van der Heijde D, Dougados M, et al. Current evidence for the management of ankylosing spondylitis: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Ann Rheum Dis 2006;65:423–32. [12] Van den Berg R, Baraliakos X, Braun J, et al. First update of current evidence for the management of ankylosing sponddylitis with non-pharmacological
[16] [17] [18]
[19]
[20] [21]
[22]
[23] [24] [25]
[26] [27]
treatment and non-biologic drugs: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Rheumatology 2012;51:1388–96. Dagfinrud H, Kvien TK, Hagen KB. Physiotherapy interventions for ankylosing spondylitis. Cochrane Database Syst Rev 2008;23:CD002822. Dougados M, d’Agostino MA, Benessiano J, et al. The DESIR cohort: a 10year follow-up of early inflammatory back pain in France: study design and baseline characteristics of the 708 recruited patients. Joint Bone Spine 2011;78:598–603. Claudepierre P. Spondyloarthritis: a window of opportunity? Joint Bone Spine 2014;81:197–9. Wendling D, Claudepierre P, Prati C. Early diagnosis and management are crucial in spondyloarthritis. Joint Bone Spine 2013;80:582–5. Calin A, Porta J, Fries JF, et al. Clinical history as a screening test for ankylosing spondylitis. JAMA 1977;237:2613–4. Rudwaleit M, Metter A, Listing J, et al. Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria. Arthritis Rheum 2006;54:569–78. Swinkels IC, Wimmers RH, Groenewegen PP, et al. What factors explain the number of physical therapy treatment sessions in patients referred with low back pain: a multilevel analysis. BMC Health Serv Res 2005;24: 74. Calin A. Can we define the outcome ok ankylosing spondylitis and the effect of physiotherapy management? J Rheumatol 1994;21:184–5. Tubach F, Ravaud P, Martin-Mola E, et al. Minimum Clinically important improvement and patient acceptable symptom state in pain and function in rheumatoid arthritis, ankylosing spondylitis, chronic back pain, hand osteoarthritis, and hip and knee osteoarthritis: results from a prospective multinational study. Arthritis Care Res 2012;64:1699–707. Anderson JJ, Baron G, van der Heijde D, et al. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum 2001;44:1876–86. Rosenbaum PR. The central role of the propensity score in observational studies for causal effects. Biometrika 1983;70:41–55. Austin PC. The performance of different propensity score methods for estimating marginal hazard ratios. Stat Med 2013;32:2837–49. Harder VS, Stuart EA, Anthony JC. Propensity score techniques and the assessment of measured covariate balance to test causal associations in psychological research. Psychol Methods 2010;15:234–49. Doran MF, Brophy S, Mackay K, et al. Predictors of longterm outcome in ankylosing spondylitis. J Rheumatol 2003;30:316–20. Cansu DU, Calisir C, Savas Yasas U, et al. Predictors severity and functional disability in Turkish patients with ankylosing spondylitis. Clin Rheumatol 2011;30:557–62.
Please cite this article in press as: Escalas C, et al. Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort. Joint Bone Spine (2015), http://dx.doi.org/10.1016/j.jbspin.2015.05.008