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Clinical Rheumatology Aug 2021Radiographic axial spondyloarthritis (also known as ankylosing spondylitis [AS]) is a chronic immune-mediated arthritis characterized by inflammation of the axial...
Radiographic axial spondyloarthritis (also known as ankylosing spondylitis [AS]) is a chronic immune-mediated arthritis characterized by inflammation of the axial skeleton, peripheral joints, and entheses. It is estimated that 1 in every 200 people are affected by AS, making it an important healthcare and socioeconomic issue. In this review, we aim to explore the current understanding of AS risk factors and provide a comprehensive update. Multiple search strings were used to identify articles of interest published in PubMed between January 1, 2013, and February 1, 2021. On the basis of the literature review and analysis, we present up-to-date information on the risk factors of developing AS and our viewpoints on disease onset and progression. Multiple genetic and nongenetic risk factors have been suggested in the onset of AS. HLA-B27 is known to have a strong association with the disease, but other genes have been implicated in disease development. Aside from genetics, other factors are thought to be involved; up to 70% of patients with AS have subclinical intestinal inflammation, suggesting that the origin of the disease may be in the gut. The exact mechanism by which AS onset begins is most likely complex and multifactorial. Key Points • It remains unclear how interactions between genes, microbes, mechanical stress, gender, and other environmental and lifestyle factors predispose patients to the development of ankylosing spondylitis (AS). • The exact mechanisms of AS are complex and multifactorial which will require much future research • Recognizing the risk factors, as well as understanding gene-environment interactions, may offer valuable insights into the etiology of AS and have important implications for diagnosis and treatment strategies.
Topics: HLA-B27 Antigen; Humans; Inflammation; Risk Factors; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 33754220
DOI: 10.1007/s10067-021-05679-7 -
Seminars in Arthritis and Rheumatism Feb 2016Despite Level 1b evidence and international consensus that exercise is beneficial in ankylosing spondylitis (AS), there is a paucity of detailed information to guide... (Review)
Review
OBJECTIVE
Despite Level 1b evidence and international consensus that exercise is beneficial in ankylosing spondylitis (AS), there is a paucity of detailed information to guide exercise prescription, including the type and dosage of exercise required for the most benefit. This collaborative project, combining evidence with clinical expertise, was established to develop practical recommendations to guide sustainable exercise prescription for individuals with AS.
METHODS
Using a modified Delphi technique, 10 clinical questions were generated and a systematic literature review was conducted for each. Draft recommendations were developed at a 2-day meeting, based on the integration of evidence summaries and expert opinion. Feedback was obtained from patient and health professional groups prior to finalisation.
RESULTS
Recommendations and practice points were developed for the following areas: assessment; monitoring; safety; disease management; AS-specific exercise; physical activity; dosage, adherence and setting. A framework was developed that could also be adapted for exercise in other chronic musculoskeletal conditions. Feedback suggests that the final consensus statement provides useful information for those seeking to provide best practice exercise prescription for people with AS.
CONCLUSION
The recommendations provide an up-to-date, evidence-based approach to the full range of issues related to the use of exercise in AS, as well as identifying evidence gaps for further research. Most importantly, this includes investigation of aspects of exercise programme design required to produce the largest effect, long-term adherence with exercise programs and the specific exercise requirements of sub-groups of people with AS. Widespread dissemination and implementation of the guidelines will be required to optimise exercise outcomes.
Topics: Consensus; Evidence-Based Medicine; Exercise Therapy; Humans; Spondylitis, Ankylosing
PubMed: 26493464
DOI: 10.1016/j.semarthrit.2015.08.003 -
Frontiers in Immunology 2022Modern pharmacological research found that the chemical components of are mainly curcumin and turmeric volatile oil. Several recent randomized controlled trials (RCT)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Modern pharmacological research found that the chemical components of are mainly curcumin and turmeric volatile oil. Several recent randomized controlled trials (RCT) have shown that curcumin improves symptoms and inflammation in patients with arthritis.
METHODS
Pubmed, Cochran Library, CNKI, and other databases were searched to collect the randomized controlled trials (RCTs). Then, the risk of bias of RCTs were assessed and data of RCTs were extracted. Finally, RevMan 5.3 was utilized for meta-analysis.
RESULTS
Twenty-nine (29) RCTs involving 2396 participants and 5 types of arthritis were included. The arthritis included Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Osteoarthritis (OA), Juvenile idiopathic arthritis (JIA) and gout/hyperuricemia. Curcumin and Curcuma longa Extract were administered in doses ranging from 120 mg to 1500 mg for a duration of 4-36 weeks. In general, Curcumin and Curcuma longa Extract showed safety in all studies and improved the severity of inflammation and pain levels in these arthritis patients. However, more RCTs are needed in the future to elucidate the effect of Curcumin and Curcuma longa Extract supplementation in patients with arthritis, including RA, OA, AS and JIA.
CONCLUSION
Curcumin and Curcuma longa Extract may improve symptoms and inflammation levels in people with arthritis. However, due to the low quality and small quantity of RCTs, the conclusions need to be interpreted carefully.
Topics: Arthritis, Rheumatoid; Curcuma; Curcumin; Humans; Inflammation; Osteoarthritis; Plant Extracts; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing
PubMed: 35935936
DOI: 10.3389/fimmu.2022.891822 -
Healthcare (Basel, Switzerland) Jan 2022This study aimed to evaluate the safety and effectiveness of non-pharmacological interventions supervised by a physiotherapist in patients with Ankylosing Spondylitis,... (Review)
Review
This study aimed to evaluate the safety and effectiveness of non-pharmacological interventions supervised by a physiotherapist in patients with Ankylosing Spondylitis, PROSPERO Protocol number CRD42020209453. Five databases (PubMed, PEDro, Scopus, Web of Science Core, and EMBASE) and reference lists with relevant articles were searched. Randomised controlled trials (RCTs) on the effectiveness of non-pharmacological interventions supervised by a physiotherapist were compared with usual care or home-based exercise programmes. Two investigators independently screened eligible studies. A total of 12 RCTs satisfied eligible criteria. The risk of bias ranged between medium and high. The meta-analysis results indicated that between supervised physiotherapy and usual care, the former was significantly associated with improvement in disease activity (standardised mean difference = -0.37, 95% CI, -0.64; -0.11; < 0.001, I = 71.25%, = 629), and functional capacity (standardised mean difference = -0.36, 95% CI, -0.61; -0.12, < 0.05; = 629). No statistically significant differences emerged when interventions were compared with home-based exercise programmes. Supervised physiotherapy is more effective than usual care in improving disease activity, functional capacity, and pain in patients with ankylosing spondylitis. No significant improvements emerged when supervised physiotherapy and home-based exercise programmes were compared. Further investigation and RCTs with larger samples are needed.
PubMed: 35052296
DOI: 10.3390/healthcare10010132 -
Annals of the Rheumatic Diseases Jan 2023To update the evidence on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with axial spondyloarthritis (axSpA) to inform... (Review)
Review
Efficacy and safety of biological DMARDs: a systematic literature review informing the 2022 update of the ASAS-EULAR recommendations for the management of axial spondyloarthritis.
OBJECTIVE
To update the evidence on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2022 update of the Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA.
METHODS
Systematic literature review (2016-2021) on efficacy and safety of bDMARDs in axSpA (radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)). Eligible study designs included randomised controlled trials (RCTs), strategy trials and observational studies (the latter only for safety and extra-musculoskeletal manifestations). All relevant efficacy/safety outcomes were included.
RESULTS
In total, 148 publications were included. Efficacy of golimumab and certolizumab was confirmed. Tumour necrosis factor inhibitor (TNFi) biosimilar-originator equivalence was demonstrated. RCT (n=15) data on efficacy of interleukin-17 inhibitors (IL-17i) demonstrated clinically relevant effects (risk ratio vs placebo to achieve ASAS40 response 1.3-15.3 (r-axSpA, n=9), 1.4-2.1 (nr-axSpA, n=2)). Efficacy of secukinumab/ixekizumab was demonstrated in TNFi-naïve and TNFi-inadequate responders. IL-23 and IL-12/23 inhibitors (risankizumab/ustekinumab) failed to show relevant benefits. Tapering of TNFi by spacing was non-inferior to standard-dose treatment. The first axSpA treat-to-target trial did not meet its primary endpoint, but showed improvements in secondary outcomes. No new risks were identified with TNFi use in observational studies (data lacking for IL-17i). Secukinumab (n=1) and etanercept (n=2) were associated with increased risk of uveitis in observational studies compared to monoclonal TNFi.
CONCLUSIONS
New evidence supports the efficacy and safety of TNFi (originators/biosimilars) and IL-17i in r-axSpA and nr-axSpA, while IL-23i failed to show relevant effects. Observational studies are needed to confirm long-term IL-17i safety.
PROSPERO REGISTRATION NUMBER
CRD42021257588.
Topics: Humans; Non-Radiographic Axial Spondyloarthritis; Antirheumatic Agents; Spondylarthritis; Certolizumab Pegol; Axial Spondyloarthritis; Biosimilar Pharmaceuticals; Tumor Necrosis Factor Inhibitors; Spondylitis, Ankylosing; Treatment Outcome
PubMed: 36270657
DOI: 10.1136/ard-2022-223298 -
Archives of Physical Medicine and... Feb 2018To assess the effectiveness of exercise programs on disease activity and function in ankylosing spondylitis (AS) by a systematic review and meta-analysis of randomized... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the effectiveness of exercise programs on disease activity and function in ankylosing spondylitis (AS) by a systematic review and meta-analysis of randomized controlled trials (RCTs).
DATA SOURCES
Medline via PubMed and Cochrane Library.
STUDY SELECTION
Reports of RCTs examining the effectiveness of exercise programs for AS published up to May 2017.
DATA EXTRACTION
Outcomes were evolution of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) after the completion of exercise programs. Modalities of exercise were compared and the use of biologic therapy was reported.
DATA SYNTHESIS
After screening 190 abstracts, we selected 26 reports for detailed evaluation and finally investigated 8 trials that assessed a home-based exercise program (2/8), swimming (1/8), Pilates training (1/8), or supervised exercises (4/8), for a total of 331 patients with AS. Four trials included patients receiving antitumor necrosis factor therapy. All trials except one showed a decrease in BASDAI and BASFI with exercise. The weighted mean difference was -0.90 (95% confidence interval, -1.52 to -0.27; I=69%; P=.005) for the BASDAI and -0.72 (95% confidence interval, -1.03 to -0.40; I=0%; P<.00001) for the BASFI in favor of exercise programs.
CONCLUSIONS
Despite the small number of patients and the heterogeneity of exercise programs in the RCTs included in this meta-analysis, its results support the potential of exercise programs to improve disease activity and body function in AS.
Topics: Exercise Therapy; Humans; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing
PubMed: 28860095
DOI: 10.1016/j.apmr.2017.07.015 -
The Cochrane Database of Systematic... Oct 2019Exercise programmes are often recommended for managing ankylosing spondylitis (AS), to reduce pain and improve or maintain functional capacity. (Review)
Review
BACKGROUND
Exercise programmes are often recommended for managing ankylosing spondylitis (AS), to reduce pain and improve or maintain functional capacity.
OBJECTIVES
To assess the benefits and harms of exercise programmes for people with AS.
SEARCH METHODS
We searched CENTRAL, the Cochrane Library, MEDLINE Ovid, EMBASE Ovid, CINAHL EBSCO, PEDro, Scopus, and two trials registers to December 2018. We searched reference lists of identified systematic reviews and included studies, handsearched recent relevant conference proceedings, and contacted experts in the field.
SELECTION CRITERIA
We included reports of randomised controlled trials (RCT) of adults with AS that compared exercise therapy programmes with an inactive control (no intervention, waiting list) or usual care.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
We included 14 RCTs with 1579 participants with AS. Most participants were male (70%), the median age was 45 years (range 39 to 47), and the mean symptom duration was nine years. The most frequently used exercises were those designed to help improve strength, flexibility, stretching, and breathing. Most exercise programmes were delivered along with drug therapy or a biological agent. We judged most of the studies at unclear or high risk of bias for several domains. All 14 studies provided data obtained immediately upon completion of the exercise programme. The median exercise programme duration was 12 weeks (interquartile range (IQR) 8 to 16). Three studies (146 participants) provided data for medium-term follow-up (< 24 weeks after completion of the exercise programmes), and one (63 participants) for long-term follow-up (> 24 weeks after completion of the exercise programmes). Nine studies compared exercise programmes to no intervention; five studies compared them to usual care (including physiotherapy, medication, or self-management).Exercise programmes versus no interventionAll data were obtained immediately upon completion of the exercise programme.For physical function, measured by a self-reporting questionnaire (the Bath Ankylosing Spondylitis Functional Index (BASFI) scale, 0 to 10; lower is better), moderate-quality evidence showed a no important clinically meaningful improvement with exercise programmes (mean difference (MD) -1.3, 95% confidence interval (CI) -1.7 to -0.9; 7 studies, 312 participants; absolute reduction 13%, 95% CI 17% to 9%).For pain, measured on a visual analogue scale (VAS, 0 to 10, lower is better), low-quality evidence showed an important clinically meaningful reduction of pain with exercise (MD -2.1, 95% CI -3.6 to -0.6; 6 studies, 288 participants; absolute reduction 21%, 95% CI 36% to 6%).For patient global assessment of disease activity, measured by a self-reporting questionnaire (the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scale, 0 to 10, lower is better), moderate-quality evidence showed no important clinically meaningful reduction with exercise (MD -0.9, 95% CI -1.3 to -0.5; 6 studies, 262 participants; absolute reduction 9%, 95% CI 13% to 5%).For spinal mobility, measured by a self-reporting questionnaire (the Bath Ankylosing Spondylitis Metrology Index (BASMI) scale, 0 to 10, lower is better), very low-quality evidence showed an improvement with exercise (MD -0.7 95%, -1.3 to -0.1; 5 studies, 232 participants) with no important clinical meaningful benefit (absolute reduction 7%, 95% CI 13% to 1%).For fatigue, measured on a VAS (0 to 10, lower is better), very low-quality evidence showed a no important clinically meaningful reduction with exercise (MD -1.4, 95% CI -2.7 to -0.1; 2 studies, 72 participants; absolute reduction 14%, 95% CI 27% to 1%).Exercise programmes versus usual careAll data were obtained immediately upon completion of the exercise programme.For physical function, measured by the BASFI scale, moderate-quality evidence showed an improvement with exercise (MD -0.4, 95% CI -0.6 to -0.2; 5 studies, 1068 participants). There was no important clinical meaningful benefit (absolute reduction 4%, 95% CI 6% to 2%).For pain, measured on a VAS (0 to 10, lower is better), moderate-quality evidence showed a reduction of pain with exercise (MD -0.5, 95% CI -0.9 to -0.1; 2 studies, 911 participants; absolute reduction 5%, 95% CI 9% to 1%). No important clinical meaningful benefit was found.For patient global assessment of disease activity, measured by the BASDAI scale, low-quality evidence showed a reduction with exercise (MD -0.7, 95% CI -1.3 to -0.1; 5 studies, 1068 participants), but it was not clinically important (absolute reduction 7%, 95% CI 13% to 1%) with important clinical meaningful benefitFor spinal mobility, measured by the BASMI scale, very low-quality evidence found a no important clinically meaningful improvement with exercise (MD -1.2, 95% CI -2.8 to 0.5; 2 studies, 85 participants; absolute reduction 12%, 95% CI 5% less to 28% more). There was no important clinical meaningful benefit.None of the studies measured fatigue.Adverse effectsWe found very low-quality evidence of the effect of exercise versus either no intervention, or usual care. We are uncertain of the potential for harm of exercises, due to low event rates, and a limited number of studies reporting events.
AUTHORS' CONCLUSIONS
We found moderate- to low-quality evidence that exercise programmes probably slightly improve function, may reduce pain, and probably slightly reduce global patient assessment of disease activity, when compared with no intervention, and measured upon completion of the programme. We found moderate- to low-quality evidence that exercise programmes probably have little or no effect on improving function or reducing pain, when compared with usual care, and may have little or no effect on reducing patient assessment of disease activity, when measured upon completion of the programmes. We are uncertain whether exercise programmes improve spinal mobility, reduce fatigue, or induce adverse effects.
PubMed: 31578051
DOI: 10.1002/14651858.CD011321.pub2 -
Annals of the Rheumatic Diseases Jan 2023To update the evidence of non-biological treatments for axial spondyloarthritis (axSpA), as a basis for the 2022 Assessment of SpondyloArthritis international... (Review)
Review
Efficacy and safety of non-pharmacological and non-biological interventions: a systematic literature review informing the 2022 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis.
OBJECTIVE
To update the evidence of non-biological treatments for axial spondyloarthritis (axSpA), as a basis for the 2022 Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA.
METHODS
A systematic literature review (2016-2021) on efficacy and safety of non-pharmacological and non-biological pharmacological treatments was performed, up to 1 January 2022. The research question was formulated according to the PICO format: Population: adult patients with r-axSpA and nr-axSpA; Intervention: non-pharmacological and non-biological pharmacological treatments; Comparator: active comparator or placebo; Outcomes: all relevant efficacy and safety outcomes. Type of studies included were: randomised controlled trials (RCTs), observational studies (for efficacy of non-pharmacological treatments, and safety), qualitative studies. Cohen's effect size (ES) was calculated for non-pharmacological and risk ratio (RR) for pharmacological treatments.
RESULTS
Of 107 publications included, 63 addressed non-pharmacological interventions, including education (n=8) and exercise (n=20). The ES for education on disease activity, function, mobility was small to moderate (eg. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), ES: 0.06-0.59). Exercise had moderate to high ES on these outcomes (eg.
BASDAI, ES
0.14-1.43). Six RCTs on targeted synthetic disease-modifying antirheumatic drugs (DMARDs) showed efficacy of tofacitinib, upadacitinib and filgotinib (phase 2 only) in r-axSpA (range RR vs placebo for ASAS20: 1.91-3.10), while apremilast and nilotinib were not efficacious. Studies on conventional synthetic DMARDs (n=3), non-steroidal anti-inflammatory drugs (NSAIDs, n=8) and other drugs (n=12) did not provide new evidence on efficacy/safety (efficacy of NSAIDs confirmed; limited efficacy of short-term glucocorticoids in one RCT).
CONCLUSIONS
Education, exercise and NSAIDs confirmed to be efficacious in axSpA. JAKi were proved efficacious in r-axSpA.
Topics: Adult; Humans; Spondylitis, Ankylosing; Spondylarthritis; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Axial Spondyloarthritis
PubMed: 36261247
DOI: 10.1136/ard-2022-223297 -
Expert Opinion on Drug Safety Dec 2016Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and... (Meta-Analysis)
Meta-Analysis Review
Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events. Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection). We searched Medline, Embase, and the Cochrane Library up to May 2014 to identify eligible studies in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis that evaluated anti-TNF drugs compared with placebo or no treatment. Expert opinion: Our study encompassed data from 71 randomized controlled trials involving 22,760 participants (range of follow-up: 1-36 months) and seven open label extension studies with 2,236 participants (range of follow-up: 6-48 months). Quantitative synthesis of the available data found statistically significant increases in the occurrence of any infections (20%), serious infections (40%), and tuberculosis (250%) associated with anti-TNF drug use, while the data for opportunistic infections were scarce. The quality of synthesized evidence was judged as moderate. Further evidence from registries and long-term epidemiological studies are needed to better define the relationship between anti-TNF agents and infection complications.
Topics: Adult; Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Humans; Infections; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing; Tumor Necrosis Factor-alpha
PubMed: 27924643
DOI: 10.1080/14740338.2016.1240783 -
Arthritis Care & Research Sep 2016To summarize the prevalence of spondyloarthritis (SpA) and its subtypes in the general population, and to identify demographic and methodologic characteristics that... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To summarize the prevalence of spondyloarthritis (SpA) and its subtypes in the general population, and to identify demographic and methodologic characteristics that might explain heterogeneity in prevalence estimates.
METHODS
A systematic literature search was performed to identify relevant articles. Risk of bias was assessed and data were extracted. Pooled prevalences were calculated. Potential sources of heterogeneity were explored by subgroup analysis and meta-regression analysis.
RESULTS
The prevalence of SpA ranged from 0.20% (95% confidence interval [95% CI] 0.00-0.66) in South-East Asia to 1.61% (95% CI 1.27-2.00) in Northern Arctic communities; the prevalence of ankylosing spondylitis (AS) from 0.02% (95% CI 0.00-0.21) in Sub-Saharan Africa to 0.35% (95% CI 0.24-0.48) in Northern Arctic communities; and the prevalence of psoriatic arthritis (PsA) from 0.01% (95% CI 0.00-0.17) in the Middle East to 0.19% (95% CI 0.16-0.32) in Europe. The following characteristics were significantly associated with variation in prevalence of SpA, AS, and/or PsA: proportion of females, mean age of the sample, geographic area and setting (demographic characteristics), year of data collection, case finding, and case ascertainment (methodologic characteristics). For the other SpA subgroups, too few studies were available to conduct a meta-analysis, but prevalence estimates of reactive arthritis (range 0.0-0.2%), SpA related to inflammatory bowel disease (range 0.0-0.1%), and undifferentiated SpA (range 0.0-0.7%) were generally low.
CONCLUSION
SpA is a common disease, but with large variation in reported prevalence estimates, which can partly be explained by differences in demographic and methodologic characteristics. Particularly, geographic area as well as case finding account for a substantial part of the heterogeneity.
Topics: Humans; Prevalence; Spondylarthritis
PubMed: 26713432
DOI: 10.1002/acr.22831