Physical Activity, Exercise Can Benefit Patients with RA

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While medical advances in rheumatoid arthritis (RA) have led to improvements in disease control and quality of life for patients worldwide, the rate for stable remission remains low.¹ Management of RA symptoms is traditionally accomplished through a combination of medications and nonpharmacological interventions.² This approach can prevent the development of secondary adverse health outcomes.

Two common nonpharmacologic interventions are physical therapy and physical activity. The scientific evidence for these interventions continues to grow. However, not all medical providers are aware of the benefits of physical therapy and physical activity, nor do they know when to prescribe physical therapy.^2,3

When it comes to physical therapy, physiotherapists (PTs) provide insightful knowledge. PTs rely on physical (e.g., functional, range of motion, muscle strength, or postural) and behavioristic assessments (e.g., behaviors associated with fear-avoidance beliefs) when tailoring interventions to increase bodily function or physical activity in general.^2,4-6 When a home-exercise program is prescribed, 50–65% of patients fail to adhere to the program. The presence of pain, low levels of physical activity and low self-efficacy are believed to create barriers between the patient and the desired treatment goal of increased physical activity.^7,8

A review found that clinical practice guidelines regarding physiotherapy lacked detail concerning intensity, frequency, duration and type of activity for desired effects. Despite this, guidelines keep emphasizing the importance of these nonpharmacological interventions.^2,6,9

This article describes how physical therapy, through physical activity and exercise, can benefit patients with RA and compares the impact of these nonpharmacologic interventions with outcomes of medical therapy. Further, this article highlights the clinical reasoning behind the design of exercise interventions for patients with RA.

Defining Physical Activity

The terms physical activity and exercise are often used interchangeably by patients and clinicians. However, physical activity is defined as any bodily movement produced by skeletal muscles that requires energy expenditure. This movement includes daily activities, such as walking, cycling or participating in sports.

What makes exercise different? Exercise, considered a subset of physical activity, is planned, structured and repetitive, and has a final or an intermediate objective to improve or maintain physical fitness.¹⁰ Exercise can be further divided into aerobic or anaerobic exercise. Aerobic exercise (commonly known as cardio) is low- to high-intensity exercise that relies mainly on the aerobic energy-generating process, requiring a high supply of oxygen to adequately meet energy demands. Generally, light- to moderate-intensity activities (e.g., walking, cycling or swimming) are sufficiently supported by aerobic metabolism.

Anaerobic exercise relies mainly on the anaerobic energy-generating process and causes lactate to form in the muscles. This process occurs when the supply of oxygen cannot support the energy demands in high-intensity activities (e.g., sprints or heavy lifts).

The American College of Sports Medi­cine provides lists of activities that are generally classified as aerobic and anaerobic on the basis of population data. However, like medications, one must consider patient-specific attributes, such as strength, cardiovascular fitness and metabolism, to properly describe energy expenditures for specific activities in a given patient.

Prescribing Exercise

Respecting the potency of pharmacological interventions comes naturally to healthcare providers. When prescribing medications, physicians must inform their patients of the appropriate dose, frequency and duration of medication, as well as potential side effects, alternative therapies and adverse events. This information ensures informed consent, enhances medication adherence and helps avoid or detect early adverse health effects associated with the medication.

With physical activity and exercise, the same reasoning holds true. Exercises are prescribed by informing the patient of the appropriate duration, intensity and frequency, as well as describing potential side effects and adverse events. Intensity and frequency are essentially the activity dose, and intensity refers to the desired level of energy expenditure during performance of the activity.

Data indicate that exercise and physical activity are potent interventions for managing RA symptoms and its consequences, plausibly leading to adverse health effects when poorly prescribed.¹¹ Despite the heterogeneity of exercise interventions, the rate of adverse effects is low, and drop-out rates from intervention studies are typically lower than from drug trials.^12-14

Pain

Pain is a common symptom in RA, with as many as 68–88% of patients rating pain as one of their top three priorities.¹⁵ The metabolic benefits of exercise, through down-regulating pro-inflammatory cytokines that attribute to pain, appear to outweigh the momentary increase in pain due to bio­mechanical stress.16 Many exercise studies of land-based aerobic and strength interventions reveal decreases in self-reported pain once tissue adapts. Improvements in self-perceived pain from these forms of exercise yield modest benefits (effect sizes of -0.53 [-1.09, 0.04]).⁵

As tissue adaptation occurs, activities or joint movements previously hindered by pain become possible. However, if the adaptation happens too quickly or at too great a mechanical load, pain may increase. Increased pain associated with inappropriately dosed exercise may lead to avoidance behaviors, adversely resulting in a decrease in total physical activity levels or lowering adherence to an exercise regimen.¹⁷ If the aim of an exercise intervention is to increase bone mass, lean muscle mass or increase cardiorespiratory fitness (CRF), patients need to understand how and when to modify exercise and what is acceptable as exercise-related discomfort vs. overstressing joints and soft tissue.¹⁸ Patient education can enhance adherence to exercise interventions and ensure proper modes of exercise, frequency, intensity and duration occur, as well as increase understanding of what is acceptable (i.e., typical) exercise-induced discomfort.¹⁹

RA & Cardiovascular Health

Although cardiovascular disease (CVD) events occur more frequently in patients with RA than in their healthy peers (3.43 and 0.59 per 100 person-years, respectively), traditional risk factors for CVD events seem to only partially explain this phenomenon, and specific rheumatic cytokines may explain the differences in risk.^20-22 Recently, CVD-associated fatalities have declined, and biologic therapies are being hailed as the reason for this new trend, because they appear to attenuate inflammatory markers.^23,24

A traditionally strong factor to consider in CVD risk is physical activity. Adults with RA accumulate less time spent engaged in physical activity than healthy peers (1,836 vs. 2,199 minutes per week, P=0.001).²⁵ Physically inactive patients with RA have a higher probability of a 10-year CVD event (higher systolic blood pressure, P=0.006, cholesterol, P<0.001, low-density lipoprotein, P=0.01) when compared with physically active RA subjects, suggesting that low physical activity levels may serve as an independent risk factor for CVD events in adults with RA.^6,26

Improving the lipid profile of RA patients is important to lower the risk of CVD events, and exercise training can offer this effect.^27,28 Although total time spent engaging in physical activity is of great importance, the literature on how exercise improves habitual physical activity is scarce.

Instead, exercise interventions have looked to improve the CRF profile (commonly defined as VO2 max in mL/kg/min) of RA patients, a profile historically 20–30% lower than that of healthy controls.¹¹ Not specific to RA patients, links between CRF and dyslipidemia have been noted, making interventions aimed at improving CRF interesting for attenuating the CVD risk in RA.²⁹

Results from a Cochrane review revealed that land-based aerobic exercise interventions significantly improved aerobic capacity (VO2 max in mL/kg/min) with an effect size of 0.99 (0.29, 1.68).⁵ Although water-based aerobic exercise had an overall effect size of 0.47, the effect was not significant (-0.04, 0,98), making it hard to deduce its potency.⁵ Presently, it is difficult to determine the most suitable intensity, frequency or duration for optimal CR improvements in RA, because the number of studies is low.

Disease Activity—Exercise

Disease activity in RA has clinical meaning, because patients with higher disease activity report lower quality of life and spend less time being physically active.^30,31 There are many ways of measuring disease activity in RA.³² In exercise interventions, the Disease Activity Scale (DAS-28) is commonly used. Despite its shortcomings in differentiating disease activity, studies tend to define a DAS greater than 5.1 as active disease, less than 3.2 as low disease activity and less than 2.6 as remission.^33,34 Today, it is widely considered safe to indulge in physical activity and exercise no matter the level of disease activity.³⁵

In an exercise study conducted for patients with highly active RA (7.0), the exercise group demonstrated a greater decrease in disease activity compared with the control group (effect size of 0.49 and 0.29 respectively), paving the way for more studies on physical activity and disease activity, although not all studies reveal significant positive effects.^36,37

Examining how exercise may potentially decrease RA disease activity is a relatively new focus. A randomized controlled trial of the safety of long-term, high-intensity aerobic exercise demonstrated improvements in disease activity (DAS lowered by 0.14).³⁸ However, in the aggregrate, a Cochrane review deemed the effects of land-based aerobic and strength programs on RA disease activity not significant (ES= 0.16 [-0.39, 0.06]).⁵ Many pharmacological interventions prefer to express disease activity outcomes as a percentage of study participants that reach remission or have low or active disease, making comparisons between the two fields difficult.²⁴ Attenuating inflammatory markers and increasing pain tolerance are believed effects of exercise that can influence disease activity.¹¹ However, it is hard to determine what intensity, duration or frequency is needed for a patient, because the scientific evidence is scarce.

Functional Ability & Exercise Interventions

Functional ability is often evaluated with a Health Assessment Questionnaire (HAQ), and a decrease of <0.22 is considered clinically meaningful.³⁹ The HAQ has been used as a primary outcome to evaluate the benefits of exercise interventions for several years. In a review of nine RCTs, the effects of aerobic exercise on HAQ was defined as a standardized mean difference of 0.24 ([95% CI 0.10, 0.38], P=0.001; I2=29%).⁴⁰ Marcora et al found progressive resistance strength training performed, on average, 2.5 times a week over 12 weeks resulted in increased lean muscle leg mass (by 839 grams, P<0.001) and improved modified HAQ scores by -0.25.⁴¹ However, another study found little to no effect on daily functioning (multi-dimensional HAQ) following an exercise intervention.¹⁸

Rheumatoid Cachexia

Rheumatoid cachexia (RC), a feature of RA, is a down-regulated state of anabolic muscle growth.⁴² Suspected culprits are malnutrition, suppressed IGF regulation, circulating pro-inflammatory cytokines (such as CRP and IL-6) and inadequate physical activity.^43,44 RC may be present in as many of 53% of adults with RA.⁴⁵

Traditionally, BMI has been the focus of CVD risk in RA patients, because a high BMI is associated with increased relative risk of CVD in the presence of obesity (RR=1.16; 95% CI 1.03, 1.29).⁴⁶ A low BMI can also increase the risk of CVD events (hazard ratio [HR] 3.34, 95% confidence interval [95% CI] 2.23–4.99).⁴⁷ Many exercise interventions were designed to normalize the BMI of RA subjects. However, BMI may not be a suitable measure of RC; among women with RA, 88.9% had a normal BMI.⁴⁸ Thus, lean body mass may be a more suitable measure to use. It is unclear how the presence of RC affects the risk of CVD in RA, because prospective studies are lacking.⁴⁹

Improving lean muscle mass can be achieved through tailored strength exercise at 80% of one repetition maximum, twice a week for 24 weeks, yielding small effects (ES=0.28), but the physical exertion of these interventions comes with an increased energy expenditure that may accentuate aspects, such as malnutrition, if not adequately prescribed.¹⁸ At a three-year follow-up, the improvements in muscle mass experienced by the exercise group did not persist, indicating that supervision may play a big role in the exercise-treatments of RC.⁵⁰

The Cost of Treating RA

In a clinical setting, exercise interventions should be administrated by a specialist in the field of activity-related physiology. Although doctors specialize in the field of pharmaceuticals, physiotherapists are often regarded as experts because they have the background in exercise science, pathology and movement science.

When reviewing the benefits of exercise in RA, it is imperative to look at treatment costs. In a review, the biologic infliximab was cost effective to less than 1% if willingness to pay was set to $50,000/QALY.⁵¹ In early RA, the cost range of $27,346–44,881 per QALY was found for TNF antagonists, and a simple hand-strengthening program was $23,857 per QALY.⁵² Cost-effectiveness studies are scarce in nonpharmaceutical trials, but the few that exist are interesting. This is an area in need of further research.

One must consider patient-specific attributes, such as strength, cardiovascular fitness & metabolism, to properly describe energy expenditures for specific activities in a given patient.

Prescribe Exercise with Competence

The effects and potency of exercise and physical activity should not be underestimated when caring for patients with RA, but it cannot be prescribed without competence. A poorly dosed physical activity intervention can be counterproductive and enforce pain avoidance behaviors that make future exercise interventions problematic, if not impossible.¹⁷

Encouraging physical activity and exercise as main components of disease management is essential in clinical communications with patients. However, ensuring these interventions are prescribed properly is paramount.

Physical therapy is a suitable option for these patients. PTs are able to evaluate patient needs and prescribe appropriately tailored exercise and physical activity interventions at the correct dose and duration.

August Flodén, PT, is a physiotherapist in the Department of Physical Therapy at Kullbergska Sjukhuset, Sweden. Having completed his master’s thesis in public health, he is currently working as a research assistant at Karolinska Institute, Stockholm. His research interests are the effects of vigorous exercise on joint inflammation, quality of life and comorbidity in adults and children with rheumatoid arthritis.

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