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Is High Intensity Exercise Appropriate For Those Dealing with Axial Spondyloarthritis (axSpA)?


The short and sweet answer is, yes, it is ok for folks dealing with these issues to exercise at higher intensities (cardiorespiratory and/or resistance training). However, we will dive into the research on the topic while addressing common myths and fears surrounding exercise for these populations in hopes to bring clarity to the discussion.


Introduction

Figure 1 - Divisions of Skeleton System

Axial spondyloarthritis (axSpA) is an umbrella phrase for chronic inflammatory issues affecting the axial spine (see Figure 1). Such disorders include:

  • Ankylosing Spondylitis

  • Psoriatic arthritis

  • Reactive arthritis, and

  • Inflammatory bowel-related arthritides (Crohn’s and Ulcerative Colitis).

The prevalence of axSpA is between 0.32% and 1.4%. Sieper 2017 Although this is a low prevalence rate, this population still necessitates evidence based interventions to aid with disease activity and quality of life. Often, issues with low prevalence rates have a lack of research and thus evidence based information to aid with decision making; further intensifying the need for well conducted trials.


Clinical Presentation:


Patients may report persistent spinal pain usually involving the low back & pelvis. Typical features include morning stiffness that is relieved with activity but not rest, as well as night pain. Admittedly, there is heterogeneity in subjective reporting from patients, and other issues may present with a similar history as well, making the diagnosis difficult. Axial spondyloarthritis can present with changes to the sacroiliac (SI) joints and/or spine visible on X-ray (e.g., in ankylosing spondylitis) or without X-ray findings altogether. The latter situation is termed non-radiographic axial spondyloarthritis. Sieper 2017 The primary issue with axSpA is inflammation, which may result in spinal structural changes leading to decrements in mobility (defined as the ability to move). Hoyer 2018 Other common presentations include inflammatory involvement of peripheral body regions, such as lower extremity joint swelling (e.g., knees), enthesitis (inflammation where ligaments and tendons attach to bone), and uveitis (inflammation of the uvea, portion of the eye).


Conservative Management:


Exercise has previously been demonstrated to have a small but beneficial effect on

disease activity for this patient population. Sveaas 2017 However, the dosage typically recommended to those dealing with axSpA is low. Many clinicians are fearful of recommending high-intensity exercise to this patient population for fear of eliciting a flare-up in symptoms and/or disease activity. Given that exercise appears to be under-dosed for these patients, perhaps the historically observed benefits of exercise could be improved with higher dosed exercise interventions.


Recent Research:


A recent study by Sveaas et al set out to determine the effects of a 12-week exercise intervention inclusive of high intensity cardiorespiratory and strength training on disease activity and cardiovascular health among participants with axSpA.


Participants were recruited from outpatient rheumatology departments and via social media advertisements in Norway and Sweden. Study inclusion was based on the following:

  • Meeting the Assessment of SpondyloArthritis International Society (ASAS) criteria for axSpA,

  • Between the ages of 18 - 70 years old,

  • No change in Tumor Necrosis Alpha (TNF)-inhibitor use during the previous 3 months

  • Moderate - High disease activity at pre-screening based on a score greater than or equal to 3.5 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and

  • No regular engagement of cardiorespiratory and strength training in prior 6 months (no more than 1/week).

Study exclusion criteria were:

  • Symptoms of Cardiovascular Disease (see table 1)

  • Comorbidities resulting in reduction in exercise capacity and/or contraindications to exercise based on the American College of Sports Medicine guidelines

  • Inability to participate in weekly exercise sessions

  • Pregnancy

Table 1 - Cardiovascular Disease Exclusionary Screen

Originally 100 participants were part of a 3 month assessor-blinded two-armed

multicenter randomized controlled trial comparing standard care (no intervention) and high intensity exercise. Three participants were lost to follow-up, leaving 97 included in the analyses. No significant baseline differences were identified between groups. The exercise protocol followed ACSM guidelines for recommended cardiorespiratory and strength training (see Tables 2A & B). The exercise intervention group had 3 training sessions each week; 2 physiotherapist-supervised sessions inclusive of cardiorespiratory and strength training, and a single session of cardiorespiratory training on their own. To ensure exercise adherence, the physiotherapist maintained a record and participants kept an exercise diary.

Table 2A: Exercise Program (3 months)

Table 2B: Exercise Program (3 months)

Of note, the participants were allowed to exercise with tolerable pain levels; defined as less than or equal to 5 on a scale of 0 to 10. If participants pain symptoms worsened the day after a training session, then adaptations were made to the exercises.


The control group was instructed to continue with their usual physical activity level and received “standard care”. A retrospective questionnaire was administered to the control group to assess exercise habits during the intervention period. Safety of participants was monitored by assessing disease flare-ups post-intervention. Assessment was based on disease activity via the Ankylosing Spondylitis Disease Activity Score (ASDAS), BASDAI, and the blood inflammatory markers C-reactive protein and erythrocyte sedimentation rate (ESR). Physiotherapists were also tasked with reporting any adverse events.


Outcomes


Baseline outcome measurements were taken at the beginning of the study and again immediately following the intervention period. Outcomes assessed included: ASDAS, BASDAI, and a clinical examination by an assessor who was blinded to group randomization. The clinical examination consisted of resting HR, blood samples, flexibility tests, and a treadmill test. The primary outcome of interest was disease activity based on the ASDAS and BASDAI.


The ASDAS includes a composite score from C-reactive protein plus 4 patient-reported variables measured on an 11-point numeric rating scale:

  1. Neck/back/hip pain

  2. Peripheral joint pain

  3. Duration of morning stiffness

  4. Patient global assessment

The ASDAS uses the following classification system:

  • Inactive disease <1.3

  • Low disease activity 1.3-2.1

  • High disease activity 2.1-3.5

  • Very high disease activity >3.50

The minimum clinically important difference (MCID) for ASDAS is 1.1 units for “clinically important improvement” and 2.0 units for “major improvement”. Magrey 2019


Similar to the ASDAS, the BASDAI is a questionnaire consisting of 5 patient reported symptoms measured on an 11-point numeric rating scale:

  1. Fatigue

  2. Neck/back/hip pain

  3. Peripheral joint pain

  4. Tenderness

  5. Degree/length of morning stiffness

Once the above variables were measured, a sum score from 0 to 10 was calculated ( 0 = no disease activity and 10 = very active disease). MCID for those reporting a BASDAI >4 (potentially high disease activity) is 1.1 as well as a minimal 50% change. Magrey 2019


Secondary outcomes included assessment of physical function via the Bath AS

Function Index (BASFI). The BASFI is a series of questions rated on an 11-point

numeric rating scale (0 - 10, with 10 = worst) and a sum score calculated.


Participants spinal mobility was also assessed via the Bath AS Metrology Index (BASMI), which consists of five measurements for spinal mobility rated on a numeric rating scale of 0 to

10.

  1. tragus-to-wall distance,

  2. cervical rotation,

  3. lateral spinal flexion and

  4. intermalleolar distance.

A mean score is calculated from the five measurements equaling a final score of 0 to 10 (10 = worst).


Cardiorespiratory fitness was measured via a maximal treadmill test based on the Balke protocol (see online supplementary file 3 for explanation). At the end of the treadmill test, peak oxygen uptake (VO2peak mL/kg/min) was estimated.


Waist circumference, BMI, and lean body mass (via a dual-energy X-ray absorptiometry scan) were also assessed. Finally, blood samples were completed after 4 hours of fasting for measurement of CRP and ESR levels.


The authors defined improvement based on ASAS20/40:

ASAS20 is defined as a relative improvement of ≥20% and an absolute improvement of ≥1 unit in at least three of the four following domains; patient global assessment, pain, physical function and morning stiffness, and no worsening of ≥20% and ≥1 unit in the remaining domains. ASAS40 response is defined as a relative improvement of ≥40% and an absolute improvement of ≥2 unit in at least three of the four domains that are defined for ASAS20, and no worsening at all in the fourth domain. Sveaas 2019

The authors calculated a necessary sample size of 100 participants. The randomization process was computer generated and participants were allocated to a group after the physiotherapist assessment. The outcome assessor was blinded to group allocation, however participants and physiotherapist supervising exercise were not, and this likely wouldn’t have been possible.


Results


The ASDAS demonstrated a between group difference of 23% (see table 3). The

exercise group had a 27% change from baseline to the end of the exercise

intervention (3 months) vs a 4% change in the control group (2.7 to 2.6). The

BASDAI demonstrated a 24% between group difference (see table 3) with a 33%

difference between baseline and intervention for the exercise group vs 9%

difference for the control group.

ASAS20/40 Improvements:


Absolute increased benefit (AIB) was 42% (95% CI, 25% to 58%) at the end of the

intervention. AIB is the calculated difference between the proportion of participants

having a 20% and 40% ASAS improvement due to the intervention. 25 patients (52%) in the exercise group and five patients (10%) in the control group achieved a 20% improvement. Additionally, the numbers needed to treat (NNT) for a positive benefit of the intervention for one additional patient was 3 (95% CI, 2 to 4).

AIB was 33% (95% CI, 19% to 48%) at the end of the intervention for 18 patients (38%) in the exercise intervention group vs 2 (4%) in the control group with 40% improvement. This improvement also demonstrates an NNT of 3 (95% CI, 2 to 5).

Figure 2 displays standardized mean difference (SMD, effect sizes) with

95% CI.

  • 0.2 - 0.4 = small effect size

  • 0.5 - 0.7 = medium effect size

  • ≥0.8 = large effect size

Fatigue, morning stiffness, neck/back/hip pain, patient global score of disease

activity, BASDAI, and ASDAS all demonstrated large effect sizes favoring the

exercise intervention.


Secondary Outcomes


Secondary outcomes demonstrated further support for the exercise intervention.

Cardiorespiratory fitness had an 8.2% between group difference in VO2peak; estimated mean gro


up difference of 2.7 (95% CI, 1.6 to 3.8). Other variables showing improvement included physical function (BASFI) with a 27% between group difference (38% vs 11%), and flexibility with a 10% between group difference (14% vs 4%). See table 4 for secondary outcomes.

Adverse Events


One patient from the exercise group experienced chest pain and nausea during the

intervention, prompting the p


erson to switch to moderate intensity exercise under the guise of their cardiologist. Additionally, only two patients reported persistent pain during the exercise intervention. This finding should help stifle some of the claims surrounding the supposed dangers of higher intensity exercise among such populations.


Big Picture


Physical activity (PA) is highly recommended for those dealing with axial

spondyloarthritis. The 2018 European League Against Rheumatism recommends


...physical activity should be an integral part of standard care for people with RA/SpA/HOA/KOA. Osthoff 2018

However, the authors listed a primary directive for future research “to evaluate the long-term effectiveness of PA at different intensities and types and monitoring of adverse events (AE). ”


As mentioned earlier, Sveaas et al conducted a 2017 systematic review on the effects of cardiorespiratory and strength training for this patient population and found small, but beneficial effects for disease activity scores, joint damage, symptoms, and erythrocyte sedimentation rate with no effect on C-reactive protein. Sveaas 2017


In the most recent Sveaas article, the authors argue perhaps only a small effect was seen due to the under dosing of exercise interventions. Although many are advocating for exercise in this cohort, little is known about the appropriateness of higher intensity exercise and many healthcare professions shy away from recommending this type of exercise for fear of worsening disease activity and

eliciting flare-ups, despite there appearing to be no strong evidence at this time to

recommend against such activities.


In their most recent article, Sveaas et al effectively demonstrated the positive benefits of high intensity cardiovascular and strength training by observing improved disease activity in this patient population as well as improved cardiorespiratory fitness via improved VO2peak, potentially leading to a reduction Cardiovascular disease (CVD) risk.


CVD risk is something to consider for this population given prior research has

demonstrated an increased risk of heart attacks and strokes. Mathieu 2018


According to Sveaas et al, those dealing with axSpA have also been demonstrated to have lower cardiorespiratory fitness than the general population. The authors argue their study demonstrates an important effect on cardiorespiratory fitness and CVD risk,

In the present study, the mean treatment effect of 2.7 mL in VO2peak indicates large health gain, as it has been reported that every 1 mL increase is associated with a 15% decrease in CV death. Sveaas 2019

Additional strengths of this article include being a clinician conducted randomized

control trial demonstrating the effectiveness of this intervention in clinical practice. The study also utilized well-supported subjective and objective outcome measurements. Adherence for this study is also considered good given thirty eight patients (76%) from the exercise intervention group maintained compliance with ≥80% of the exercise protocol. Only four patients stopped the exercise intervention. Activity in the control group was likely not a major confounder given only five (10%) patients in the control group completed cardiorespiratory or strength training (≥2/week) during the three month intervention. The study also had a low drop out rate. Finally, the NNT is considered low (3) demonstrating a minimal reach for future positive effects in patients.


Limitations


The exercise intervention didn’t meet the recommended MCID of 1.1 for the ASDAS. However, the effect sizes for the intervention were large for both primary outcome measures (ASDAS and BASDAI). Another limitation is that the study was only 3 months in duration. It would be interesting to see if the beneficial effects of higher intensity exercise were sustained, magnified, or attenuated with a longer duration, as well as being able to assess long term changes in disease activity.


Furthermore, the authors appear to be arguing for a positive effect on

the inflammatory process by affecting CRP. The measured CRP remained the same in the exercise intervention group but worsened by 1 unit in the control group. Whether this should be considered as evidence for positive effect on blood inflammatory markers is debatable, given that blood ESR remained the same for both groups. A longer study duration may provide more insight on the effects of higher intensity exercise on blood inflammatory markers.


The authors also bring up a good point about the potential confounding effects on

reported outcome measures due to the increased contact time between clinician and patients for the exercise intervention compared to the control group. Continued

interaction can likely play a role in positive psychological effects on the exercise

intervention group and thus improved reported outcomes/symptoms.


Finally, resistance exercise dosage likely needs further study for this patient population. It is debatable whether the exercise guidelines outlined in Table 2B for muscular strength exercises should be considered of high intensity. The cardiovascular exercise recommendations have clear cut explanations based on heart rate for measuring intensity levels (as denoted by 4 x 4 intervals at 90-95% of maxHR), as well as an objective marker of improvement in cardiorespiratory fitness as measured by VO2peak. However, such standards are lacking in the muscular strength exercise guidelines and no strength based objective measurement was utilized. Of note the authors did utilize a DEXA scan to track lean body mass changes between groups, but examining table 3 above - there doesn’t appear to be any significant effects in the exercise group vs the control group besides waist circumference (which this may be predisposed to a sampling bias given the inclusion criteria for data analysis for this variable). This likely speaks to the underdosing of the strength training protocol.


The authors appear to have utilized circuit training with no rest allowed between each resistance training exercise. The intensity appears capped at 8-10 repetition maximum and 20 minutes allotted for completion. Progression was based on the patient’s ability to complete more than 10 reps with a particular weight. However, we are unsure of how these standards measure up to a percentage of the patient’s estimated 1RM (e1RM) or internal perception of difficulty of the exercise, typically measured via Rate of Perceived Exertion (RPE).


A recent article by Morton et al discusses current best practices for improving strength and hypertrophy. Although fully discussing this topic is beyond the

scope of this article, the authors highlight several relevant factors when designing a

resistance training protocol with the goals of improving strength and/or hypertrophy.


Changes in muscle mass and strength are mediated by the FITT principles

  • Frequency: more sessions per week may mediate (volume-dependent) muscle size

  • Intensity (effort): volitional fatigue and internal focus increase muscle size

  • Type: exercise selection and high loads mediate muscle strength

  • Time: performing more repetitions (volume) may mediate muscle size

  • Other variables (e.g., inter-set rest, time under tension) have little influence on outcomes Morton 2019

However, this study is a step in the right direction and a case can be made the protocol utilized is a sufficient first step in non-trained/minimally-trained individuals. Further long-term follow-up would help fine-tune the appropriate dosage recommendations to improve disease activity, quality of life, and performance markers in this population.


Sveaas et al conclude,

We conclude that high intensity exercise should be strongly considered as a part of treatment of axSpA. Future studies should examine the effects of longer exercise interventions with longer follow-up. It is also time to refine the high intensity exercise programme in clinical practice. Sveaas 2019

Overall I’m in agreement with this conclusion and the authors did demonstrated positive effects with high intensity exercise training in those dealing with axial spondyloarthritis.


Hopefully evidence such as this will continue to dispel fear based misinformation

regarding exercise recommendations for those dealing with axial spondyloarthritis.


References:


  1. Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet (London, England). 2017; 390(10089):73-84.

  2. Hoyer EH, Young DL, Klein LM, et al. Toward a Common Language for Measuring Patient Mobility in the Hospital: Reliability and Construct Validity of Interprofessional Mobility Measures. Physical therapy. 2018; 98(2):133-142

  3. Magrey M, Ritchlin C. Measuring outcomes in ankylosing spondylitis Current Opinion in Rheumatology. 2019; 31(2):109-117.

  4. Rausch Osthoff AK, Niedermann K, Braun J, et al. 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis. Annals of the rheumatic diseases. 2018; 77(9):1251-1260.

  5. Sveaas SH, Smedslund G, Hagen KB, Dagfinrud H. Effect of cardiorespiratory and strength exercises on disease activity in patients with inflammatory rheumatic diseases: a systematic review and meta-analysis. British journal of sports medicine. 2017; 51(14):1065-1072.

  6. Mathieu S, Soubrier M. Cardiovascular events in ankylosing spondylitis: a 2018 meta-analysis. Annals of the rheumatic diseases. 2018.

  7. Morton, Robert & Colenso-Semple, Lauren & Phillips, Stuart. (2019). Training for Strength and Hypertrophy: An Evidence-based Approach. Current Opinion in Physiology. 10.1016/j.cophys.2019.04.006.

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