| |

Received: 18 May 2020    Revised: 24 July 2020    Accepted: 7 August 2020

DOI: 10.1111/jan.14574

RE VIE W PAPER

The effect of physical exercise on rheumatoid arthritis: An

overview of systematic reviews and meta-analysis

Huiling Hu1 | Anqi Xu1 | Chao Gao2 | Zhenqing Wang3 | Xue Wu1,4

1
School of Nursing, Peking University,
Beijing, P.R. China
2
Department of Rheumatology and
Immunology, The People's Hospital of
Peking University, Beijing, P.R. China
3
Department of Rheumatology and
Immunology, Peking University Third
Hospital, Beijing, P.R. China
4
Health Science Centre for Evidence-Based
Nursing: A Joanna Briggs Institute Centre of
Excellence, Peking University, Beijing, P.R.
China
Correspondence
Xue Wu, School of Nursing, Peking
University, 38 Xueyuan Road, Haidian
District, Beijing, P.R. China.
Email: wuxue@bjmu.edu.cn
Funding information
This research was funded by the National
Natural Science Foundation of China (grant
no. 71601004) and Peking University
Langtai Nursing Research Fund (grant no.
LTHL19MS03).
Abstract
Aims: To determine which outcomes will be improved by different exercise interven-
tions and the evidence quality for each intervention.
Design: Overview of systematic reviews and meta-analysis.
Data Sources: PubMed, Cochrane, Web of Science, CINAHL, and Embase. Published
from the establishment of the database to 3 September 2019.
Review methods: AMSTAR 2 and PRISMA were used to evaluate methodological and
reporting quality. Evidence quality of the effect of each intervention was assessed
according to GRADE guidelines. Meta-analysis of original studies was conducted for
comparison of systematic reviews and to explore the effect of different exercise in-
terventions on the same outcome.
Results: Ten systematic reviews were included in the overview. A significant im-
provement was seen in: aerobic exercise for aerobic capacity; strength training for
erythrocyte sedimentation rate and 50-foot walking time; aerobic exercise combined
with strength training for aerobic capacity, physical function, and fatigue; hand exer-
cise for hand function.
Conclusions: For the maximum benefit of rheumatoid arthritis (RA) patients, differ-
ent exercise methods should be selected according to the symptoms. For RA pa-
tients, any exercise is better than no exercise, but the intensity, frequency, and period
of exercise for better results are not determined.
Impact: What problem did the study address is which outcomes will be improved
by different exercise interventions. For maximum benefit for RA patients, different
exercise methods should be selected according to symptoms. The research summa-
rized the evidence of exercise rehabilitation of RA and will help RA patients or their
caregivers choose the appropriate type of exercise, which will play a positive role on
the rehabilitation of patients with RA.

KEYWORDS

aerobic capacity, exercise, nursing, overview of systematic reviews, pain, physical function,
rheumatoid arthritis

Huiling Hu and Anqi Xu are Joint first authors and contributed equally to this paper.

J. Adv. Nurs. 2020;00:1–17. wileyonlinelibrary.com/journal/jan© 2020 John Wiley & Sons Ltd     1 |
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2       HU et al.
1 |  I NTRO D U C TI O N
Rheumatoid arthritis (RA) is a systemic autoimmune disease and is
one of the most common types of chronic inflammation (Smolen
et al., 2016). The main clinical manifestation is symmetrical inflam-
matory polyarthritis, but there are also extraarticular manifesta-
tions, such as lung involvement, vasculitis, and systemic syndrome
(Smolen et  al.,  2016). In 2017, there were 19,965,115 RA cases
worldwide, an increase in 7.4% since 1990 (Safiri et al., 2019). It is
more common in women and may occur at any age, with the com-
monest age of occurrence being between 50–60 years (Huizinga
& Pincus,  2010). Fatigue, arthritis, and deformity are the main
complications of RA, which lead to the impairment of body func-
tion (Englbrecht et al., 2013). Studies from different countries and
regions show that fatigue is highly prevalent in patients with RA
(40%–80%) (Lee et al., 2020). The most common symptom is pain
(Borenstein et  al.,  2010), which has a negative impact on body
function and quality of life (Boyden et  al.,  2016). RA results in a
great burden for both individuals and society, the personal bur-
den including musculoskeletal damage, quality of life decline and
risk of complications (Cross et al., 2014), the social burden includ-
ing decline in working ability and decreased social participation
(Sokka et al., 2010). The multifaceted health consequences of RA
indicate that RA management should not only focus on joint symp-
toms, but also on addressing systemic and psychosocial effects
(Metsios et al., 2015). It has been proposed that the ultimate goal
of managing RA is to prevent or control dysfunction and reduce
pain (Kwoh et al., 2002). Exercise is a promising intervention to
improve RA-related outcomes and alleviate a negative emotional
state (Osthoff et al., 2018).
At present, most RA patients have a weak sense of the im-
portance of exercise and are unwilling to do exercise for various
reasons. The Quantitative Patient Questionnaires in Standard
Monitoring of Patients with Rheumatoid Arthritis study, which in-
cluded 5,235 RA patients from 21 countries, found that only 13.8%
reported exercise at least three times/week (Sokka et al., 2008). In
addition, some people have expressed that they do not receive
enough information and advice to exercise (Larkin et  al.,  2017).
There are a large number of studies that have examined the ef-
fectiveness and safety of exercise interventions carried out in RA
patients, but these vary in duration, type of intervention, and re-
sults. The purpose of this review is to provide information for RA
patients and decision makers.
1.1 | Background
Although some health professionals have traditionally warned
against exercise in RA patients, designing appropriate exercise pro-
cedures is often beneficial and physical therapy may optimize the
functional capabilities of RA patients (Huizinga & Pincus,  2010).
The European League Against Rheumatism (EULAR) recommends
that physical activity should be a component of standard care for
people with RA (Osthoff et al., 2018). Also, there is researchers hold
in the view that a structured exercise program should be an inte-
gral part of chronic disease management protocols for patients with
RA (Azeez et al., 2020). Notably, exercise can reduce the burden of
inflammation and enhance functional ability (Metsios et  al.,  2015).
Unfortunately, patients with RA preferred sedentary behaviour
(Schouller et al., 2019), which may be due to pain, fatigue (Thomsen
et  al.,  2015), or fear of joint damage (van Zanten et  al.,  2015).
However, this behaviour can lead to more serious RA-related symp-
toms (Greene et al., 2006; Khoja et al., 2016; Prioreschi et al., 2015),
leading to a vicious circle. These data illustrate the need to promote
exercise in RA.
The types of exercise that are included in studies can be divided
into aerobic exercise, strength training, a combination of the first
two, aquatic exercise and hand exercise. Aerobic exercise is de-
signed to increase peak oxygen consumption (VO2max) by increasing
the heart rate to 50%–80% of the maximum heart rate (Verhoeven
et al., 2016), examples include jogging, walking, and cycling. Strength
training is specifically designed to increase muscle strength by gradu-
ally increasing resistance during movement (Verhoeven et al., 2016).
Aquatic exercise is carried out in warm water, which can produce
buoyancy. Therefore, it becomes a feasible choice for patients with
risk of joint trauma (Cheatham & Cain, 2015). Hand exercise includes
stretching and strengthening exercise which also plays an important
role as the hand impairments will become prevalent after two years
of onset (Horsten et al., 2010). Telescoping fingers was used to treat
a 69-year-old woman with RA presented for severe joint deformities,
which show a positive effect (Sacks, 2019). Exercise improves RA-
related outcomes through different mechanisms. Exercise reduces
the risk of cardiovascular disease, especially the development of
atherosclerosis, which may be mediated by many factors, including
increased blood flow, the improvement of antioxidant mechanisms,
and the increase of nitric oxide synthase (eNOS) activity (Metsios
et al., 2014). Exercise improves pain via increasing the expression of
β-endorphin (Fichna et al., 2007) and by inducing an anti-inflamma-
tory phenotype (Metsios & Kitas, 2018).
For RA patients, it is very important to choose the right way of
exercise. According to the systematic review we retrieved, we found
that the outcomes and interventions of these studies are different
but some overlaps. Therefore, we did this overview to determine
which outcomes will be improved by different exercise interven-
tions. Due to the duplication of the original studies included in those
systematic reviews, we also carried out a meta-analysis, to make the
results more accurate.
2 | TH E R E V I E W
2.1 | Aims
To determine which outcomes will be improved by different exercise
interventions and the evidence quality of each intervention towards
RA patients.
HU et al.
2.2 | Design
The design of this study was the overview of systematic re-
views and a meta-analysis of some studies included in those re-
views. There is no protocol and this study was conducted with
the support of the Cochrane Handbook for Systematic Reviews
of Interventions (the part of overview) (Higgins et  al.,  2019) and
reported in accordance with PRIO-harms statement (Bougioukas
et al., 2018).
2.3 | Search methods
We searched PubMed, Cochrane, Web of Science, CINAHL,
Embase and other resources for systematic reviews and meta-
analyses and published time was from the establishment of the
database to 3 September 2019. The search strategy is presented
in Appendix S1.
2.4 | Search outcomes
After removing the duplicates, one author screened articles by read-
ing the titles and abstracts. Then, two authors identified included
reviews according to the criteria as follows. The inclusion Criteria
are 1)RCTs that examined exercise in RA, 2) published in English, 3)
participants were adults with RA. The interventions were exercise
or physical activity while the comparisons were other exercise, wait-
list, usual care, or mobility exercise. We excluded reviews of RCTs
whose major intervention was non-exercise (i.e. health education,
self-management). Systematic reviews were only included if they re-
ported outcomes including but not limited to pain, physical function,
fatigue, disease activity, ESR, cardiopulmonary function, and grip
strength. Disagreement or uncertainty was resolved through discus-
sion with the third author.
2.5 | Quality appraisal
Two authors independently assessed the quality of included re-
views using AMSTAR 2 (A Measurement Tool to Assess Systematic
Reviews 2) (Shea et al., 2017). It contains 16 items, of which seven
are critical domains (item 2, 4, 7, 9, 11, 13 & 15). We rated the meth-
odological quality of reviews according to the criteria below:
1. High: no or one non-critical weakness;
2. Moderate: more than one non-critical weakness, multiple non-
critical weaknesses may diminish confidence in the review and
it may be appropriate to move the overall appraisal down from
moderate to low confidence;
3. Low: one critical flaw with or without non-critical weaknesses;
4. Critically low: more than one critical flaw with or without non-
critical weaknesses.
|
      3
Two authors independently assessed reporting quality using
PRISMA (Preferred Reporting Items for Systematic Reviews and
Meta-Analyses) (Moher, Liberati, Tetzlaff, Altman, & Grp, 2009), a
27-item checklist (Appendix S2a). Each item is evaluated according
to whether it is reported or not and receives one point for a full re-
port, 0.5 point for a partial report and 0 points for no report. Fewer
than 15 points indicates relatively serious report information de-
fects, 15–21 points indicates certain report defects and 21.5–27
points indicates a relatively complete report (An et al., 2013).
Finally, we assessed evidence quality of each intervention ac-
cording to GRADE guidelines (Balshem et  al.,  2011) and rated the
quality of evidence as high, moderate, low, or very low by means of
GRADEprofiler 3.6 (Brozek et al., 2008). The quality of an evidence
body is high if the study design is randomized, while observational
studies are low quality. We also browsed original studies when nec-
essary. When the sample size is far less than 400, according to the
grade group’ recommendation, we will degrade in aspect of impreci-
sion. When I2 of the subgroup is >50%, we think that the difference
in the point estimates of the intervention effect is too large and the
inconsistency is degraded. See Appendix  S2b for specific quality
classification methods.
2.6 | Data abstraction
We extracted data from systematic reviews using a pre-defined
data extraction form by one author and verified by another author.
Authors discussed the extraction and disagreement was resolved via
discussion with the third author. The data extracted consisted of the
first author and published year, number of included studies and par-
ticipants, intervention, outcomes, quality assessment and whether
it was a meta-analysis or not. The combined effect size was also
extracted if the review was a meta-analysis. The primary outcomes
were pain, physical function, and aerobic capacity, while the second-
ary outcomes were disease activity, ESR, fatigue, 50-foot walking
time, and grip strength.
As we found there are too many duplications of individual stud-
ies included in systematic reviews and perhaps not all outcomes of
the original study were reported in reviews. We decided to extract
the sample size, mean, and standard deviation from individual trials
of the included reviews and conduct our own meta-analysis to ex-
plore the effect of different exercise interventions on RA patients
and compare the results with the systematic reviews. More original
studies were included in our meta-analysis and we compared the
results of our meta-analysis with those of the included systematic
reviews. If the results are consistent, the reliability of the results is
enhanced, and inconsistent results will be discussed.
2.7 | Synthesis
This was a synthesis between the findings of overview of systematic
review and the meta analysis that subsequently carried out. First, we
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4       HU et al.
qualitatively summarized the intervention results of each review and
analyzed the different types of intervention, duration, and exercise
intensity. In addition, we extracted the data of systematic reviews’
meta-analysis to explain the effect of intervention better. Due to the
lack of relevant data, direct comparisons between different inter-
ventions are not available.
Second, a meta-analysis was conducted using Review Manager
5.3 to explore the effect of different interventions on the same
outcome, which was carried out using data from those meta-anal-
yses reported in the systematic reviews included in overview.
The combined effect we calculated is the standardized mean dif-
ference (SMD, 95% confidence interval) and the inverse-variance
weighting method with a random effect was used. When only me-
dian and extremum or quartiles were reported in original studies
whose mean and standard deviation (SD) could not be acquired
from the systematic reviews, we did not estimate mean or SD, be-
cause the sample size is too small for an accurate estimated value.
2
Heterogeneity was quantified by I , where a value >50% indicates
substantial heterogeneity. We excluded low-quality studies for
sensitivity analysis. We detected publication bias by Egger's test
(Egger et al., 1997).
3 |   R E S U LT S
3.1 | The results of overview
3.1.1 | Search results and study characteristics
For our overview of reviews, we retrieved 3,588 articles, of which
2,620 remained after duplicates were removed. After browsing the
title and summary, 45 potentially relevant reviews were identified.
We removed 35 studies after reading the full text, leaving a total
of 10 reviews (Baillet et  al.,  2010, 2012; Cairns & McVeigh,  2009;
Hammond & Prior,  2016; Han et  al.,  2004; Hurkmans et  al.,  2009;
Peres et al., 2017; Rongen-van Dartel et al., 2015; Salmon et al., 2017;
Williams et al., 2018) including 97 studies and 7,190 participants and
the flow diagram is shown in Figure 1. The reasons for exclusion are
summarized in Appendix S3.
3.1.2 | Quality of included reviews
According to the criteria of AMSTAR 2, all reviews were of low quality.
This is mainly because none of them provided a protocol, which is a
critical domain (Table 1). The results of PRISMA are shown in Table 2
and the detailed results in Appendix S5. Reporting quality evaluation
shows that the average score is 20.1 points (range 13–24). Among
them, one review (Cairns & McVeigh,  2009) received  ≤  15 points;
four (Baillet et  al.,  2012; Hammond & Prior,  2016; Han et  al.,  2004;
Rongen-van Dartel et al., 2015) received 15–21 points; and five (Baillet
et  al.,  2010; Hurkmans et  al.,  2009; Rongen-van Dartel et  al.,  2015;
Salmon et al., 2017; Williams et al., 2018) received >21 points.
The evidence quality grading results of each intervention are
shown in Table 3 and the detailed results in Supplementary Material.
The main cause of a low grade was risk of bias, such as lack of blinding
outcome assessors, allocation concealment, or inadequate reporting
of these. Imprecision due to small sample size is also a reason that
cannot be ignored. Furthermore, there are four evidence bodies that
are low grade due to inconsistency.
3.2 | The results of our meta-analysis
For our meta-analysis, we included 30 papers which had been re-
ported in one or more of the systematic reviews included in our
overview. We excluded 34 papers which were duplicates and 33
which did not meet the criteria. The references for these origi-
nal studies are listed in Appendix  S4. The intervention of aero-
bic exercise is studied in three reviews (Baillet et  al.,  2010; Han
et  al.,  2004; Rongen-van Dartel et  al.,  2015), including a Tai Chi
intervention (Han et  al.,  2004). Hand exercise is studied in two
reviews (Hammond & Prior,  2016; Williams et  al.,  2018) while re-
sistance exercise was examined in one review (Baillet et al., 2012).
Meta-analysis was conducted in six reviews (Baillet et  al.,  2010,
2012; Han et al., 2004; Hurkmans et al., 2009; Rongen-van Dartel
et al., 2015; Williams et al., 2018). The details of included reviews
are available in Table 2.
The results of the meta-analysis are presented in Figure 2. These
meta-analysis studies were all included in one or more systematic
reviews included in the overview. Forest plots display that aerobic
exercise plays a positive role in patients’ aerobic capacity; Strength
training plays a positive role in 50-foot walking time, pain, and ESR;
Aerobic exercise and strength training plays a positive role in aerobic
capacity, physical function, and fatigue; Hand exercise plays a posi-
tive role in grip strength.
The SMD and 95% CI were not substantially changed by ex-
cluding low-quality reviews (Dellhag et  al.,  1992; Flint-Wagner
et al., 2009; Harkcom et al., 1985; Kirsteins et al., 1991; Nordemar
et  al.,  1981; Stavropoulos-Kalinoglou et  al.,  2013) from the me-
ta-analysis (Appendix  S6). Egger's test showed that there was no
significant publication bias (p > 0.05).
3.3 | Effects of interventions for RA
The effects of each type of exercise on RA patients are listed in
Table 4 and the inconsistent results are explained in the discussion.
Table  4 summarizes the results of the meta-analyses included in
overview and the meta-analysis we did additionally.
3.3.1 | Aerobic exercise
A quantitative analysis from Baillet et al. (2010) indicated a ben-
efit of aerobic exercise on pain (SMD 0.31, 95% CI 0.06–0.55,
HU et al. |
      5

Records identified through Additional records identified

Identification

database searching through other sources

(N = 3583) (N = 5)

Records after duplicates removed

(N = 3588)
Screening

Records excluded
Records screened
(N = 968)
(N = 2620)

Full-text articles excluded, with reasons

(N = 35)
Full-text articles assessed Included in non-RCTs: 12
for eligibility Not published in English: 2
(N = 45) Not SR or meta-analysis: 7
Eligibility

Not exercise intervention: 4

Not RA patients: 10

Studies included in Full-text articles excluded, with

qualitative synthesis reasons
(N = 10) (N = 0)

Studies included in overview

Included

(N = 10)

F I G U R E 1   Study flow diagram [Colour figure can be viewed at wileyonlinelibrary.com]

p < 0.05), in accordance with (Cairns and McVeigh (2009); how-
ever, the results from Hurkmans et  al.  (2009) and our meta-
analysis indicated that there was no effect on pain. Its effect
on aerobic capacity was positive (SMD 0.99, 95% CI 0.29–1.68,
p  <  0.05) (Hurkmans et  al.,  2009), which is consistent with our
meta-analysis (SMD 0.90, 95% CI 0.25–1.56, p < 0.05). As for fa-
tigue, there was a positive effect when intervention duration was
3 months (SMD −0.31, 95% CI −0.55 to −0.06); but there was no
significant effect after 6 months. There was no impact on physi-
cal function, 50-foot walking time, grip strength, ESR, or disease
activity.
3.3.2 | Strength training
Only one review (Han et al., 2004) reported a positive effect of strength
training on pain, consistent with our meta-analysis (SMD 0.61, 95% CI
−0.98 to −0.24, p < 0.05). However, the analysis of Baillet et al. (2012)
reported no impact. These same authors reported that strength train-
ing could reduce 50-foot walking time (WMD −0.91, 95% CI −2.95 to
−0.85, p < 0.05), consistent with our meta-analysis (SMD −0.90, 95%
CI −1.58 to −0.23, p < 0.05). However, strength training had no effect
on physical function or aerobic capacity. There was an inconsistent
result for grip strength. Baillet et al. (2012) reported a positive effect
 |
6      

TA B L E 1   Methodological quality of included reviews

Author (year)

Rongen-
Baillet Baillet Cairns Hammond Han Hurkmans Peres van Dartel Salmon Williams
Questions (2012) (2010) (2009) (2016) (2004) (2009) (2017) (2015) (2017) (2018)

1. Did the research questions and inclusion Yes Yes No Yes Yes Yes No Yes No Yes
criteria for the review include the
components of PICO?
2. Did the report of the review contain an No No No No No No No No No No
explicit statement that the review methods
were established prior to the conduct of
the review and did the report justify any
significant deviations from the protocol?a 
3. Did the review authors explain their No No No No No No No No No No
selection of the study designs for inclusion
in the review?
4. Did the review authors use a Partial yes Partial yes Partial yes Partial yes Partial Partial yes Partial yes Partial yes Partial yes Partial yes
comprehensive literature search strategy?a  yes
5. Did the review authors perform study No No No Yes No No Yes No No Yes
selection in duplicate?
6. Did the review authors perform data Yes No No No Yes Yes Yes No No Yes
extraction in duplicate?
7. Did the review authors provide a list No No Yes Yes Yes Yes No No No No
of excluded studies and justify the
exclusions?a 
8. Did the review authors describe the No Partial Yes Partial Yes Partial Yes Partial Partial Yes Partial Yes Partial Yes Partial Yes Partial Yes
included studies in adequate detail? Yes
9. Did the review authors use a satisfactory Partial Yes Partial Yes Partial Yes Partial Yes Partial Partial Yes Partial Yes Yes Yes Yes
technique for assessing the risk of bias Yes
(RoB) in individual studies that were
included in the review?a 
10. Did the review authors report on the No No No No No No No No No No
sources of funding for the studies included
in the review?
11. If meta-analysis was performed did the No Yes No meta- No meta-analysis No Yes No meta- Yes No meta- Yes
review authors use appropriate methods analysis analysis analysis
for statistical combination of results?a 

(Continues)
HU et al.
 HU et al.

TA B L E 1   (Continued)

Author (year)

Rongen-
Baillet Baillet Cairns Hammond Han Hurkmans Peres van Dartel Salmon Williams
Questions (2012) (2010) (2009) (2016) (2004) (2009) (2017) (2015) (2017) (2018)

12. If meta-analysis was performed, did the Yes Yes No meta- No meta-analysis Yes Yes No meta- Yes No meta- No
review authors assess the potential impact analysis analysis analysis
of RoB in individual studies on the results
of the meta-analysis or other evidence
synthesis?
13. Did the review authors account for RoB Yes No No No Yes Yes Yes Yes No Yes
in individual studies when interpreting/
discussing the results of the review?a 
14. Did the review authors provide a Yes No No No Yes Yes No Yes No Yes
satisfactory explanation for, and discussion
of, any heterogeneity observed in the
results of the review?
15. If they performed quantitative synthesis Yes Yes No meta- No meta-analysis No No No meta- No No meta- No
did the review authors carry out an analysis analysis analysis
adequate investigation of publication bias
(small study bias) and discuss its likely
impact on the results of the review?a 
16. Did the review authors report any Yes No No No No No Yes Yes Yes Yes
potential sources of conflict of interest,
including any funding they received for
conducting the review?
Quality rating Critically low Critically low Critically Critically low Critically Critically Critically Critically Critically low Critically
low low low low low low
a
Critical items.
|
      7
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8      

TA B L E 2   The characteristics of included reviews

Number studies Meta- PRISMA

Author/year Participants (participants) Intervention Outcome Quality assessment analysis score

Baillet (2012) Adult patients 10 (547） Resistance exercise Physical function; disease activity; Jadad Yes 21
with RA pain; ESR
Baillet (2010) Adult patients 14 (1,040) Aerobic Exercise Physical function; disease activity; Jadad Yes 23
with RA pain
Cairns (2009) adult patients 18 (1,312) Aerobic exercise; strength exercises; Physical function 10 criteria modified from No 13
with RA combinations of both; aquatic exercise the Delphi list
Hammond (2016) adult patients 4 (665) Hand exercise Hand function; pain; grip strength PEDro No 17
with RA
Han (2004) adult patients 4 (206) Aerobic exercise (Tai Chi) Physical function; grip strength Jadad Yes 17
with RA
Hurkmans (2009) adult patients 8 (575) Aerobic capacity; strength training Physical function; pain; aerobic The 8-point scale of Yes 23
with RA capacity; disease activity methodological criteria
Peres (2017) adult patients 19 (842) Physical activity and cryotherapy Aerobic capacity; disease activity; Methodological-quality No 17
with RA pain index
Rongen-van Dartel adult patients 5 (570) Aerobic exercise Fatigue The Cochrane risk of bias Yes 24
(2015) with RA tool
Salmon (2017) adult patients 8 (540) Physical activity Fatigue The Cochrane risk of bias No 22
with RA tool
Williams (2018) adult patients 7 (839) Hand exercise Hand function; pain; grip strength The Cochrane risk of bias Yes 24
with RA tool

Abbreviations: ESR, erythrocyte sedimentation rate; RA, rheumatoid arthritis.

HU et al.
HU et al. |
      9

(MD 26.4 95% CI 12.3–40.5, p < 0.05) whereas Cairns and McVeigh TA B L E 3   Quality of evidence
(2009) reported no impact. Finally, strength training had no impact on
Quality of
disease activity from the results of quantitative analyses, although the Outcomes evidence (GRADE)
effect was positive in a qualitative review (Cairns & McVeigh, 2009).
Aerobic exercise for RA
However for ESR, it is an optimistic method (Baillet et al., [2012]: MD
Pain Very low
−5.17, 95% CI −8.77 to −1.58, p < 0.05; our meta-analysis: SMD −0.54,
Physical function Low
95% CI −0.95 to −0.12, p < 0.05).
Aerobic capacity Very low
Disease activity Low

3.3.3 | Aerobic exercise and strength training ESR Very low

Fatigue Very low

Pain could not be reduced by this mode of exercise, as shown by the Grip strength Very low
results of one review (Hurkmans et al., 2009) and the meta-analysis 50-foot walking time Very low
we did. However, aerobic exercise combined with strength training is Strength training for RA
an effective way to improve the aerobic capacity of RA patients. This Pain Very low
is supported by two quantitative analyses (Hurkmans et al., [2009] Physical function Very low
SMD 0.46, 95% CI 0.22–0.70, p < 0.05; and our meta-analysis: SMD
Disease activity Low
0.78, 95% CI −0.01 to 1.57, p  <  0.05) and two qualitative results
ESR Very low
(Cairns & McVeigh, 2009; Peres et al., 2017). This mode of exercise
50-foot walking time Very low
had no impact on aerobic capacity when carried out with low inten-
Aerobic exercise and strength training for RA
sity (Peres et al., 2017). Peres et al. (2017) draw the conclusion from
Pain Low
two trials that it showed a positive correlation with grip strength at
either high or low intensity. From our meta-analysis, this exercise Physical function Moderate

type can significantly improve fatigue (SMD −0.31, 95% CI −0.52 Aerobic capacity Low

to −0.10, p < 0.05). Its effect on function was positive in our meta- Disease activity Moderate
analysis (SMD −0.43, 95% CI −0.76 to −0.10, p < 0.05), in contrast ESR Low
with the “no impact” results of Hurkmans et al. (2009). There was no Fatigue Low
effect on ESR or disease activity. Aquatic exercise
Pain Moderate
Physical function Moderate
3.3.4 | Aquatic exercise Aerobic capacity Low
Hand exercise
Aquatic exercise did not reduce pain or DAS (disease activity score) in
Pain Moderate
the review by Hurkmans et al. (2009) or our meta-analysis. However,
Disease activity Low
it was positively related to aerobic capacity (SMD 0.47, 95% CI −0.04–
Grip strength Low
0.98, p < 0.05) after 6 months’ intervention. However, there was no
impact on aerobic capacity, physical function, or disease activity. Abbreviations: ESR, erythrocyte sedimentation rate; RA, rheumatoid
arthritis.

3.3.5 | Hand exercise
Qualitative analysis showed that hand exercise has a positive ef-
fect on pain, consistent with the result of a 3-month intervention
(Williams et al., 2018) (MD −27.98, 95% CI −48.93 to −7.03, p < 0.05).
Grip strength was found to be improved by hand exercise over
6  months(Hammond & Prior,  2016) or even 3  months (Williams
et al., 2018) (left hand: MD 0.44, 95% CI 0.11–0.78, p < 0.05; right
hand: MD 0.46, 95% CI 0.13–0.80, p < 0.05). However, the impact
decreased with time duration. Our meta-analysis showed some evi-
dence of a positive effect (SMD 0.19, 95% CI 0.00–0.38, p = 0.05).
As for hand function, the effect is positive (3–12 months: MD 4.50,
95% CI 1.58 to 7.42, p < 0.05; >12 months: MD 4.30, 95% CI 0.86–
7.74, p  <  0.05 (Williams et  al.,  2018)). Hand exercise has positive
effects on disease activity if duration is <6 months, but there was no
significant effect after 6 months.
To summarize, aerobic exercise can improve aerobic capacity
significantly, but it has no marked effect on grip strength, 50-foot
walk time and physical function. Its effect on pain and fatigue
is uncertain. Strength training is effective in improving ESR and
50-foot walk time but has no effect in improving aerobic capacity
or physical function. Its effect on pain, grip strength, and disease
activity is uncertain. Aerobic exercise combined with strength
training has a promising effect on aerobic capacity, physical
function, and fatigue, but no effect on ESR or disease activity.
Its effect on pain is uncertain. Aquatic exercise has no impact on
pain, physical function or disease activity. Its effect on aerobic
 |
10       HU et al.

F I G U R E 2   (a) The effect on pain. (b) The effect on physical function. (c) The effect on aerobic capacity. (d) The effect on disease activity.
(e) The effect on ESR. (f) The effect on fatigue. (g) The effect on grip strength. (h) The effect on 50-foot walking time [Colour figure can be
viewed at wileyonlinelibrary.com]

capacity is uncertain. Hand exercise is an effective method to im- different interventions towards RA and the authors thought that
prove hand function, but its effect on grip strength and pain is there was not enough information to judge whether exercise is
uncertain. One review (Salmon et al., 2017) did not describe the effective for fatigue in RA.
HU et al.
F I G U R E 2   continued
4 | D I S CU S S I O N
In this study we carried out an overview of systematic reviews fol-
lowed by an additional meta-analysis of trials which had been in-
cluded in the reviews to determine which outcomes will be improved
by different exercise interventions and the evidence quality of each
intervention towards RA patients. We conducted an additional
meta-analysis including more original studies than individual sys-
tematic reviews and compared the results with those of the included
systematic reviews. If the results are consistent, the reliability of the
results is enhanced. Inconsistent results will be discussed below.
First, we will discuss the causes of inconsistent results, which cause
uncertainty as to whether an intervention is valid in terms of the primary
outcomes. As for aerobic exercise towards pain in RA, our meta-anal-
ysis found two reviews with different results. Cairns and McVeigh
(2009) drew a positive conclusion from an original study, which was
also included in our meta-analysis. Baillet et al. (2012) drew a positive
|
      11
conclusion included six trials in their meta-analysis, two of which used
a net-based exercise intervention (vandenEnde et al., 1996) and did not
report standard difference (Hansen et al., 1993). Neither of those two
articles were included in our meta-analysis and therefore we cannot
definitively say that aerobic exercise has a significant effect on pain.
The next variable was strength training on pain, whose result differs
across meta-analyses. The duration of each intervention varies widely,
which we think is the cause of the difference. Therefore, the effect
needs further research. The third aspect is aquatic exercise on aerobic
capacity. The review of Hurkmans et al. (2009) included studies whose
participants are RA and osteoarthritis patients, but they did not per-
form separate analyses. Therefore, the result from our meta-analysis is
maybe more reliable. The fourth type is aerobic exercise combined with
strength training for pain and function. In this aspect, the exercise pa-
rameters vary too greatly to form a conclusion. For example, one type is
a multi-activity exercise which is a complete scheme including warming
up, muscle strength, aerobic exercise, and cool down.
 |

TA B L E 4   Efficacy of exercise for RA

12      

50-foot walking Physical Disease

Author (year) Aerobic capacity Grip strength time Pain function Fatigue ESR activity

Aerobic exercise
Baillet (2010) / / / Positive / / / No impact
Cairns (2009) Positive No impact / Positive / / / /
Hurkmans (2009) (<6 months) Positive / / No impact No impact / / No impact
Peres (2017) Positive / / / / / / /
Rongen-van Dartel (2015) (12 weeks) / / / / / Positive / /
Rongen-van Dartel (2015) (24 weeks) / / / / / No impact / /
Han (2004) (Tai Chi) / No impact No impact / No impact / / /
a
Our meta-analysis   Positive No impact No impact No impact No impact No impact no impact No impact
Strength training
Baillet (2012) / Positive Positive No impact / / Positive No impact
Cairns (2009) / No impact / / / / Positive Positive
Peres (2017) No impact / / Positive / / / /
Our meta-analysis / / Positive Positive No impact / Positive No impact
Aerobic exercise and strength training
Cairns (2009) Positive / / / / / No impact No impact
Hurkmans (2009) (<6 months) / / / No impact No impact / / /
Hurkmans (2009) (≥6 months) Positive / / No impact / / / No impact
Peres (2017) (high intensity) Positive Positive / Positive / / / /
Peres (2017) (low intensity) No impact Positive / / / / No impact /
Our meta-analysis Positive (p = 0.05) / / No impact Positive Positive / No impact
Aquatic exercise
Hurkmans (2009) (<6 months) Positive / / No impact / / / No impact
Our meta-analysis No impact / / No impact No impact / / /
Hand exercise (hand function)
Hammond (2016) (<6 months) / Positive / Positive Positive / / Positive
Hammond (2016) (≥6 months) / Po impact / Positive Positive / / No impact
Williams (2018) (<3 months) / Positive / Positive / / / /
Williams (2018) (3–12 months) / No impact / No impact Positive / / /
Williams (2018) (>12 months) / No impact / No impact Positive / / /

(Continues)
HU et al.
HU et al. |
      13

Second, the quality of evidence is mostly low or very low, due to

No impact
bias and small sample sizes. The allocation concealment and blinding

Disease
activity
of assessors should be emphasized in future research. In addition,
many outcomes are self-reported by patients, who are not likely to

/
be blinded in the trial. Using objective indicators to evaluate pain
can be tried, which has been used in previous trials (Perruchoud
et al., 2014).
ESR Third, different exercise intensities and intervention durations
will produce different results. Moderate-high intensity, of 60% to
/

/
85% of maximal heart rate, was more likely to have a positive im-
pact on cardiovascular-related outcomes if physical conditions per-
mit (Hurkmans et al., 2009). In addition, higher efficacy trends were
Uncertain

observed in studies with resistance ≥80% load (Baillet et al., 2012).

Fatigue

This was also confirmed by research of Lange et  al.  (2017), who
carried out exercise with medium-high intensity. It is important to
/

note that the intensity of exercise depends on the severity of the

affected joint (Cheatham & Cain,  2015). Caution should be taken
when recommending high-intensity exercise in patients with high
function
Physical

baseline joint injury (Cairns & McVeigh,  2009). As to duration of

intervention, the short-term (<6  months) effect of a home exer-
/

cise program is stable, but the long-term (> 6 months) effect is not
clear, which may be related to patient compliance (Hammond &
Prior, 2016). In an overview on the effects of exercise on chronic
No impact

pain, long-term exercise (>12  months) is recommended because

Pain

it is more conducive to managing and controlling pain (Geneen

/

et al., 2017).
50-foot walking

It is worth noting that any form of exercise will not aggravate

disease activity and ESR, which to some extent shows that exer-
cise is safe for RA, which is consistent with the results of Azeez
time

et  al.  (2020). The combination of aerobic exercise and strength

/

training is also recommended (Cairns & McVeigh, 2009; Hurkmans

et al., 2009). Regular participation in dynamic exercise can help im-
Grip strength

prove joint range of motion, muscle strength, aerobic capacity, and

(p = 0.05)
Positive

physical function without increasing fatigue and joint symptoms

(Neuberger et al., 1997). The results of this study on pain and fatigue
/

are also consistent with a qualitative review (Katz et al., 2020).

Aerobic capacity

4.1 | Limitations
The meta-analysis conducted by overview authors.

There are several limitations of our overview. First, studies that re-
/

ported median, quartiles or extremum values were not included in

No classified description of exercise mode.

our meta-analysis, which is likely to introduce inaccuracies. Secondly,

we did not explore the psychological impact of exercise. Negative
emotions, especially stress, tend to exacerbate the symptoms of the
disease (Duda & van Zanten, 2010) and patients’ self-efficacy is re-
TA B L E 4   (Continued)

lated to medication compliance (Spruill et al., 2014). A quantitative

Our meta-analysis

synthesis of evidence from RCTs showed that exercise had a posi-

Salmon (2017)b 

tive effect on anxiety and depression in people with RA (McKenna

Author (year)

et al., 2018). Therefore, it is worthy of study in the future.

There are several other research directions for the future.
The first is the risk factors of cardiovascular disease (CVD), such
as insulin resistance, hypertension, and hypercholesterolemia,
b
a
 |
14       HU et al.
which play an important role in the occurrence of cardiovascu-
lar events in RA patients (Metsios et al., 2015). There is evidence
that increasing physical activity and/or engaging in aerobic and
resistance exercise programs are effective interventions to sig-
nificantly reduce CVD risk in RA (Hornberg et al., 2020; Metsios
et  al.,  2020) and aerobic capacity is a strong and independent
predictor of cardiovascular disease (Stavropoulos-Kalinoglou
et al., 2013). So encouraging exercise among RA patients is a good
method of reducing that risk. The second is the determination of
exercise parameters (i.e. frequency, intensity, period, duration,
and mode). In the studies in our review, the results of different
experiments are different and the exercise parameters used were
also different. Thus, it is difficult to accurately judge the effect of
exercise on RA patients. It is necessary to determine a suitable
exercise program. Randomized controlled trials with different ex-
ercise parameters are a desirable way to determine the best pa-
rameters (Baillet et al., 2010). Thirdly, we can study the influence
of exercise on the blood indexes of RA patients, such as inflamma-
tory markers, which is beneficial for understanding the mechanism
of the effect of exercise and can help us to design more scientific
exercise programs. Besides, such measurements provide objective
data. Last but not least, the cost-effectiveness of exercise for RA
patients needs to be further explored. Some researchers think that
although exercise programs are more expensive than usual care,
quality-adjusted life years are significantly increased (Hammond &
Prior, 2016). However, specific research in this area is rare.
5 |  CO N C LU S I O N
In conclusion, for the maximum benefit of RA patients, different ex-
ercise methods should be selected according to the symptoms. For
RA patients, any exercise is better than no exercise, but the intensity,
frequency, and period of exercise for better results are not deter-
mined. For RA patients with different symptoms, we need to cus-
tomize the appropriate specific exercise program in next step, that is
to determine the exercise parameters to maximize the effect under
the premise of safety.
C O N FL I C T O F I N T E R E S T
There is no conflict of interest statement.
PEER REVIEW
The peer review history for this article is available at https://publo​
ns.com/publo​n/10.1111/jan.14574.
ORCID
Xue Wu  https://orcid.org/0000-0001-7407-5257
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S U P P O R T I N G I N FO R M AT I O N
Additional supporting information may be found online in the
Supporting Information section.
How to cite this article: Hu H, Xu A, Gao C, Wang Z, Wu X.
The effect of physical exercise on rheumatoid arthritis: An
overview of systematic reviews and meta-analysis. J. Adv.
Nurs. 2020;00:1–17. https://doi.org/10.1111/jan.14574
HU et al. |
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