Mortality in spondylarthritis

doi:10.1016/j.jbspin.2011.02.012

Joint Bone Spine

Volume 78, Issue 5, October 2011, Pages 466-470

https://doi.org/10.1016/j.jbspin.2011.02.012 Get rights and content

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory joint disease that can lead to chronic pain in axial and peripheral joints and to functional impairments after several years. Excess mortality has been reported in patients with AS. We reviewed recent studies of patients with AS who were treated and monitored according to the improved methods developed in the past few years, without radiation therapy. Our results do not support excess mortality in these patients. Long-term follow-up data from patients enrolled in biologics registries will provide additional information. Cardiovascular disease is the leading cause of death in patients with AS, as in the general population. However, the cardiovascular mortality rate may be slightly increased in patients with AS, probably as a result of dyslipidemia and early endothelial dysfunction. Similarly, and as expected, there is excess mortality related to the spinal disease itself and to renal and gastrointestinal disease. More surprisingly, alcohol abuse and injury or suicide cause excess mortality compared to the general population. In the absence of radiation or radium-224 therapy, and regardless of the other treatments used, the evidence does not support an increased rate of lymphoma or other malignancies compared to the general population. In this review, we discuss the causes and rates of mortality in patients with AS.

Introduction

Ankylosing spondylitis (AS) is a chronic inflammatory joint disease that can lead to chronic pain in the axial and peripheral joints and to functional impairments after several years. Excess mortality has been reported in patients with AS. The musculoskeletal manifestations of AS include inflammatory and structural abnormalities such as syndesmophytes, erosions, vertebral fractures and fusion, sacroiliitis, and enthesitis. Some patients have peripheral arthritis. AS is a systemic disease that can cause extraarticular manifestations including aortitis, cardiac conduction disturbances, interstitial lung disease, secondary amyloidosis, inflammatory bowel disease, ocular abnormalities, and psoriasis or other skin lesions.

Several studies and review articles [1], [2] suggest excess mortality among AS patients. Excess mortality has also been documented in RA patients, although major differences exist between AS and RA populations. As with RA, the excess mortality in AS is ascribed to an increase in fatal cardiovascular events.

Here, we reviewed published data on mortality rates and causes of death among patients with AS. The available data are not yet sufficient for a comparison of standardized mortality ratios (SMRs) with and without TNFα antagonist therapy for AS.

Section snippets

Is ankylosing spondylitis associated with excess mortality?

The two main tools used to evaluate excess mortality in populations with AS are the SMR, or ratio of observed mortality on expected mortality in the general population of same age and sex distribution, and survival curve analysis. The results vary with the date and location of the studies and with changes in treatment strategies over time. In early studies, radiotherapy or intravenous radium-224 was used for pain relief. These treatments were associated with excess mortality (SMR, 1.45) related

Cardiovascular disease

Cardiovascular disease was consistently identified as the leading cause of death (Table 2), although the excess risk compared to the same-age general population was modest. Recent studies established that inflammatory joint disease was associated with an increased risk of atheroma development, perhaps related in part to the chronic systemic inflammation [11]. However, whereas systemic inflammation is often marked in RA, it is usually moderate in AS. Nevertheless, a study of 27 patients with AS

Conclusion

Our literature review does not provide clear evidence of excess mortality among AS patients not given radiotherapy. Mortality may be increased compared to the general population among AS patients with disease durations longer than 20 years. However, studies of patients followed-up into the 1990s fail to suggest a significant difference with the general population. It can be hoped that these results will be confirmed in the near future. A number of specific causes of death are responsible for

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

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Les consultations pluridisciplinaires avec implication du pharmacien pourraient optimiser le parcours de soin et la prise en charge des patients ambulatoires traités par biothérapies sous-cutanée. D’ores et déjà les patients ont exprimé leur satisfaction pour ce parcours de soins et le retour sur investissement est positif.
Biologics (bDMARDs) have revolutionized the prognosis of patients with inflammatory arthritis, but are not without serious side effects. The patient must be able to identify them, acquire self-care abilities or skills and adhere to their treatment. Multidisciplinary consultations, including a pharmaceutical consultation could improve the care of these patients. The pharmaceutical presence make it easier to switch to a biosimilar with etended patient support thanks to the community-hospital network. The return on investment is possible thanks to the more frequent use of biosimilars and the pricing of this type of consultation by the “Forfait de Prestation Intermédiaire”.
Eligible patients are patients with rheumatoid arthritis or spondyloarthritis, treated with subcutaneous bDMARDs. The criteria assessed were patient's knowledge of their biotherapy using the Biosecure score, their medication adherence using the CQR-5, the total of switch to biosimilars perform and the financial statement of the consultations. An assessment of the actions deployed for the community-hospital network.
Two hundred and ninety-five patients (47.4%) benefited multidisciplinary consultation. The mean score of the Biosecure score was 69.6/100 (moderate knowledge) and 261 patients (88.5%) were highly adherent. 57 patients (73%) accepted the switch to biosimilar. 197 pharmacy were contacted, all of witch for patients who receive the switch. Overall patient's satisfaction was 26.9/28.
Multidisciplinary consultations with involvement of the pharmacist should optimized patient care and the management of outpatients treated with bDMARDs. Patients have already expressed their satisfaction with this course of care and the return on investment is positive.
World mortality of ankylosing spondylitis, psoriatic arthritis and inflammatory bowel disease in 2015 and its evolution from 2001 to 2015
2022, Joint Bone Spine
There is little epidemiological data on global mortality in spondyloarthritis (SpA) and inflammatory bowel disease. We then determined mortality rates of ankylosing spondylitis (AS), psoriatic arthritis (PsA), Crohn's disease (CD) and ulcerative colitis (UC) both globally and by country, and to describe their evolution between 2001 and 2015.
We used mortality data from the World Health Organisation (WHO), which shows the number of deaths classified by age, sex, and cause of death coded by ICD-10. Age-standardized mortality rates (ASMR) were constructed using the 2015 WHO reference population. Temporal trend analyses of ASMR were performed between 2001 and 2015 using joinpoint regression.
Global ASMR was for 0.13 [0.11–0.14] deaths per million inhabitants for AS, 0.04 [0.03–0.05] for PsA, 0.86 [0.82–0.89] for CD and 0.76 [0.73–0.79] for UC. The worldwide trend analysis showed no significant change in ASMR for AS, a statistically significant increase from 2004 to 2015 (mean annual percent change (APC): 5.94%, p < 0.001) for PsA, and a statistically significant decrease from 2001 to 2015 for CD (mean APC: −0.82%, p < 0.001) and UC (mean APC: −1.29%, p < 0.001). Statistically significant geographical disparities were identified.
We found significant geographical disparities in SpA and IBD mortality across the world. Further studies seem to be needed to better understand the evolution of mortality over the last twenty years.
Balneotherapy in spondyloarthropathy: A systematic review
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To evaluate the effectiveness of balneotherapy on spondyloarthritis.
Two authors independently searched the CENTRAL, MEDLINE, SCOPUS, EMBASE and WEB OF SCIENCE databases until July 2017, for randomized controlled trials published in French or English, that included participants, and interventions: adults with spondyloarthritis, treated by balneotherapy program or one of its components and compared with any other intervention or no treatment. Internal validity, external validity, quality of the statistical analysis, and publication bias were systematically evaluated. We report the best level of evidence.
Nine articles were selected; the internal validity was high in two studies, average in one study, and low in six studies. With high internal validity, one study found a difference for pain between immersion in radon-rich water and tap water for the whole population or rheumatic disease, but the BASFI is not improved for the subgroup of patients with spondyloarthritis. The other study with high validity reported a significant 28-week improvement in quality of life and a composite index. In a study with moderate internal validity involving ankylosing spondylitis patients with associated with inflammatory bowel disease, a balneotherapy program demonstrated a relevant clinical improvement when compared to patients on waiting list. With low internal validity, TNFa inhibitors + spa therapy were found to be superior to a treatment with TNFa inhibitors alone in patients with psoriatic arthritis.
Two trials with high validity demonstrated improvements, but this systematic review is not sufficient to prove the efficacy of balneotherapy in spondyloarthritis. More trials are needed with larger sample size to confirm the preliminary results observed and conclusively determine the benefits of balneotherapy.
Effects of non-manipulative osteopathic management in addition to physical therapy and rehabilitation on clinical outcomes of ankylosing spondylitis patients: A preliminary randomized clinical trial
2020, Journal of Bodywork and Movement Therapies
Citation Excerpt :
Ankylosing spondylitis (AS) is a chronic inflammatory disease that is frequently accompanied by spinal back pain, joint stiffness and loss of spinal mobility. These clinical aspects may lead to various functional impairments, deterioration of the quality of life, loss of productivity at work as well as to a diminished social life (Boonen et al., 2001; Prati et al., 2011; Zochling et al., 2006). Regarding conservative management physical therapy seems to be the most common care to improve function and clinical outcomes by showing benefits of therapeutic education, daily flexibility exercises, strength and aerobic training, and pain reduction (Passalent et al., 2010; Rosu et al., 2014; Zochling et al., 2006).
Ankylosing Spondylitis (AS) is reported to impair quality of life, physical and functional ability of patients. Rehabilitation and physical therapy is usually proposed to improve AS patient clinical conditions. Besides, an osteopathic management has not been extensively studied in the field of inflammatory diseases. =
To investigate the effects of osteopathic approach in addition to conventional rehabilitation management on clinical and functional outcomes among patients with AS.
Eighteen patients with AS were recruited to participate to a physical therapy and rehabilitation (PTR) program over an 18-week period. They were randomly allocated into two groups to complete PTR only or PTR combined with osteopathic management without manipulative techniques (OSTEO group). Thoracolumbar maximal isometric strength (for flexion, extension, lateroflexion, and axial rotation) and flexibility, functional index, pain intensity and quality of life (self-assessment questionnaires) were assessed before and after the protocol.
Significant improvements were observed for the OSTEO group in strength, flexibility, disease activity and pain compared to the PTR group. However the difference between groups did not reach statistical significance for all the post-intervention measures. No significant correlation was found between functional, disability data or pain intensity and disease duration for both groups.
The results suggest that osteopathic management in addition to a physical therapy and rehabilitation program may be beneficial for individuals who suffer from AS. Further investigations are required using larger sample sizes to confirm these preliminary results.
Evaluation of the impact of a nurse-led program of systematic screening of comorbidities in patients with axial spondyloarthritis: The results of the COMEDSPA prospective, controlled, one year randomized trial
2020, Seminars in Arthritis and Rheumatism
Citation Excerpt :
SpA is a systemic multifaceted disease, which involves the axial skeleton (axial SpA, axSpA) but can also present with peripheral (i.e. peripheral arthritis, peripheral enthesitis or dactylitis) and extra-articular involvement (i.e. skin psoriasis, acute anterior uveitis or inflammatory bowel disease (IBD)) [15,16]. Patients with SpA have been reported to be at greater risk than in the general population particularly with regard to a few specific disorders (e.g. cardiovascular disease (CV) and osteoporosis). [17–19] Such increased risk in comparison to the general population can be explained both by the treatment of SpA (e.g. NSAIDs, corticosteroids) but also by other factors that may be observed in patients with SpA (e.g. metabolic syndrome, systemic inflammation).
To evaluate the impact of a nurse-led program of systematic screening for the management (detection/prevention) of comorbidities.
Prospective, randomized, controlled, open, 12-month trial (NCT02374749). Participants: consecutive patients with axial Spondyloarthritis (axSpA) (according to the rheumatologist)
A nurse collected data on comorbidities during a specific outpatient visit. In the event of non-agreement with recommendations, the patient was informed and a specific recommendation was given to the patient (orally and in a with a detailed written report). Patients were seen after one year in a nurse-led visit.
random allocation (i.e. either this program or an educational program not presented here and considered here as the control group).
: change after one year of a weighted comorbidity management score (0 to 100 where 0= optimal management).
502 patients were included (252 and 250 in the active and control groups, respectively): age: 47±12 years, male gender: 63%, disease duration: 14±11y. After one year, no differences were observed in a weighted comorbidity management score. However, the number of patients in agreement with recommendations was significantly higher in the active group for vaccinations (flu vaccination: 28.6% vs. 9.9%, p<0.01; pneumococcal vaccination:40.0% vs. 21.1%,p=0.04), for cancer screening (skin cancer screening: 36.3% vs. 17.2%, p=0.04) and for osteoporosis (bone densitometry performed: 22.6% vs. 8.7%, p<0.01; Vitamin D supplementation initiation: 51.9% vs. 9.4%, p<0.01).
This study suggests the short-term benefit of a single-visit nurse-led program for systematic screening of comorbidities for its management in agreement with recommendations, even in this young population of patients with axSpA.
Treat to target in axial spondyloarthritis: From its concept to its implementation
2020, Journal of Autoimmunity
Treat to target is defined by a process defining a level of a relevant outcome of the disease to be reached in order to prevent subsequent disability The benefit of a Treat to Target strategy has been clearly demonstrated in chronic diseases such as diabetes and hypertension.
A better knowledge of the natural history of chronic inflammatory rheumatic diseases including axial spondyloarthritis has emphasized the deleterious long term effect of a sustained inflammation, usually evaluated by disease activity markers.
The Treat to Treat strategy in axial spondyloarthritis has emerged since the possibility of getting treatments not only capable to improve the current symptomatic situation of the patient but also to prevent further deleterious irreversible hard endpoints such as disability due to structural damage or important comorbidities such as renal failure or cardiovascular diseases.
This is particularly the case for the “conventional” biologics (e.g. TNF blockers) with an experience in daily practice for at least two decades but also for more recent biologics (e.g. anti IL17 inhibitors) and for some promising targeted synthetic Disease Modifying AntiRheumatics Drugs (e.g. JAK kinase inhibitors) moreover, a part from the abrogation of inflammation, other targets can be considered such as smoking cessation, NSAID intake reduction or treatment of predisposing factors of cardiovascular diseases (e. g. hypertension, …). A Treat to Target strategy in axial spondyloarthritis has to consider the following different components:the stages of the disease, the risks of the disease, the reversible predisposing factors of the risks of the disease, the optimal threshold of the outcome measures evaluating the predisposing factors (TARGET), the time to reach the target and the necessity to maintain this success (sustainability). Moreover, the different methods/initiatives facilitating the implementation of a Treat to Target strategy in rheumatological daily practice have also to be considered (level of evidence, international recommendations, importance of the patient's participation, …).

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ReviewMortality in spondylarthritis

Abstract

Introduction

Section snippets

Is ankylosing spondylitis associated with excess mortality?

Cardiovascular disease

Conclusion

Disclosure of interest

Joint Bone Spine

Joint Bone Spine

Am J Cardiol

Mortality in ankylosing spondylitis

Clin Exp Rheumatol

Mortality, course of disease and prognosis of patients with ankylosing spondylitis

Clin Exp Rheumatol

Leukaemia and aplastic anaemia in patients irradiated for ankylosing spondylitis

Spec Rep Ser Med Res Counc (GB)

Mortality among patients with ankylosing spondylitis not given X-ray therapy

N Engl J Med

Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis

Ann Rheum Dis

Ankylosing spondylitis: survival in men with and without radiotherapy

Arthritis Rheum

Survival among patients with ankylosing spondylitis: a life-table analysis

J Rheumatol

Cancer mortality following X-ray treatment for ankylosing spondylitis

Int J Cancer

Ankylosing spondylitis in Rochester, Minnesota, 1935-1989. Is the epidemiology changing?

Arthritis Rheum

Incidence and prevalence of ankylosing spondylitis in Northern Norway

Arthritis Rheum

Accelerated atherosclerosis in inflammatory rheumatic diseases

Scand J Rheumatol

Cardiovascular risk parameters in men with ankylosing spondylitis in comparison with non-inflammatory control subjects: relevance of systemic inflammation

Clin Sci (Lond)

Hyperhomocysteinemia in ankylosing spondylitis: prevalence and association with clinical variables

Rheumatol Int

Signs of accelerated preclinical atherosclerosis in patients with ankylosing spondylitis

J Rheumatol

Impaired endothelial function in patients with ankylosing spondylitis

Rheumatology (Oxford)

Myocardial infarction and cardiovascular risk profile in ankylosing spondylitis. A systematic review and meta-analysis

Ann Rheum Dis

Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis

Circulation

Non-steroidal anti-inflammatory drug use does not appear to be associated with increased cardiovascular mortality in patients with inflammatory polyarthritis: results from a primary care based inception cohort of patients

Ann Rheum Dis

Mortality in pacemaker-treated patients. A follow-up study of the impact of HLA B27 and associated rheumatic disorders

Acta Med Scand

Risk for malignant lymphoma in ankylosing spondylitis: a nationwide Swedish case-control study

Ann Rheum Dis

Review
Mortality in spondylarthritis