The effect of axial spondyloarthritis on mental health: Results from the Atlas

1 / 19 “This is a pre-copyediting, author-produced PDF of an article accepted for publication in The Journal of Rheumatology following peer review. The definitive publisher-authenticated version [Garrido-Cumbrera, M., Delgado-Domínguez, C. J., Gálvez-Ruiz, D., Mur, C. B., & Navarro-Compán, V. (2019). The effect of axial spondyloarthritis on mental health: results from the atlas. The Journal of Rheumatology, 46(10), 1284-1289.] is available online at: https://www.jrheum.org/content/46/10/1284 ” 2 / 19 The Impact of Axial Spondyloarthritis on Mental Health: Results from the Atlas M. Garrido-Cumbrera1,2 0000-0001-9727-1189 C.J. Delgado-Domínguez1 0000-0002-9335-5841 D. Gálvez-Ruiz1 0000-0003-3292-3857 C. Blanch Mur3 ORCID N/A V. Navarro-Compán4, 0000-0002-4527-852X on behalf of the Atlas working group 1Universidad de Sevilla, 2Spanish Coordinator of Spondyloarthritis Associations (CEADE), 3Novartis Spain, 4Hospital La Paz IdiPAZ. Key Indexing Terms: Spondylarthritis, Mental Health, Depression, Anxiety Correspondence to: Prof Marco Garrido-Cumbrera, PhD, Health & Territory Research (HTR). Centro de Investigación, Tecnología e Innovación Manuel Losada Villasante. Universidad de Sevilla. C/ Doctor Rafael Martínez Domínguez, s/n. Seville 41013, Spain. E-mail: mcumbr[email protected] Funding: This study was funded by Novartis, Spain Disclosure statement: The authors have declared no conflicts of interest. Running head: Axial Spondyloarthritis Mental Health 3 / 19 Abstract Objective: To assess the risk for mental disorders in patients with axSpA and to examine the associated factors with this. Method: In 2016, a sample of 680 axSpA patients was interviewed as part of the development process for the Atlas of Axial Spondyloarthritis in Spain. The risk of mental disorders in these patients was assessed using the General Health Questionnaire (GHQ-12) scale. Additionally, the variables associated with the risk of mental disorders were investigated, including: sociodemographic characteristics (age, gender, relationship, association membership, job status, and educational level); disease status (BASDAI, spinal stiffness and functional limitation); and previous diagnosis of mental disorders (depression and anxiety). Bivariate correlation analyses were performed, followed by multiple hierarchical and stepwise regression analysis. Results: A total of 45.6% patients were at risk of mental disorders. All variables except educational level and thoracic stiffness significantly correlated with risk of mental disorder. Nevertheless, disease activity, functional limitation, and age showed the highest coefficient (r=0.543, p<0.001; r=0.378, p<0.001; r=-0.174, p<0.001, respectively). In the stepwise regression analysis, four variables (disease activity, functional limitation, association membership, and cervical stiffness) explained the majority of the variance for the risk of mental disorders. Disease activity displayed the highest explanatory degree (R2=0.875, p<0.001). Conclusions: In patients with axSpA, the prevalence of risk for mental disorders is high. Combined with a certain sociodemographic profile, high disease activity is a good indicator of the risk of for mental disorders. 4 / 19 Keywords: Axial Spondyloarthritis, BASDAI, Spinal Stiffness, Functional Limitation, Depression, Anxiety, GHQ-12. 5 / 19 INTRODUCTION Axial spondyloarthritis (axSpA) manifestations, such as loss of mobility, chronic pain and fatigue have an impact on a patient’s daily functioning and quality of life1. However, the same number and degree of manifestations does not always have the same impact on all patients. On the one hand, increasing evidence published during the last ten years has demonstrated the importance of psychosocial factors for patients adjusting to their physical limitations and chronic pain stemming from the disease2,3,4. Mental health problems, such as depression and anxiety, can worsen functioning and adherence to treatment5. A longitudinal study carried out over one year in patients with ankylosing spondylitis (AS) showed that depression is a mediating factor between the disease activity degree and functional limitation6. On the other hand, previous data suggest that the psychological health status of patients with axSpA may be influenced by the level of disease activity experienced, although these findings have not been confirmed7. A recent systematic review and meta-analysis reported that the prevalence of depression in patients with axSpA ranging from 11% to 64%8. This wide estimation in previous studies reflects the fact that very heterogeneous definitions and assessments of depression were employed in these studies. In addition, most of these studies mainly included male patients, with a very long disease duration and substantial radiographic damage and, therefore, their results are difficult to be extrapolated to all patients across the entire spectrum of axSpA. The Atlas of Spondyloarthritis 20179 is a national initiative that seeks to better understand the current state of people suffering from axSpA. It utilizes an integrative approach based on scientific evidence, expert knowledge, and patient opinion. The Atlas population represents the entire spectrum of axSpA and is equally distributed in terms of gender. Additionally, the risk of mental disorders (RMD) was assessed by using the 12-item General Health Questionnaire 12 (GHQ-12). This is a valid screening tool for identifying minor psychiatric disorders in the general population 6 / 19 within non-psychiatric clinical settings such as primary care or general medical out-patient facilities. Therefore, the Atlas 2017 provides a great opportunity to further explore the impact of disease outcomes on mental health in patients with axSpA. Moreover, the screening tool can shed light on the influence of explanatory variables related to mental health disorders in these patients. Aims and scope The objective of the present study was to determine the prevalence of risk for mental disorders in patients with axSpA and any associated factors. Our hypothesis was that greater disease activity is associated with a higher risk of suffering from mental disorders. METHODS Study design and population A sample of 680 patients diagnosed with axSpA was interviewed between 1 May and 15 August 2016 as part of the Atlas on Axial Spondyloarthritis in Spain9, which seeks to promote early diagnosis, improved healthcare, and the use of effective treatments in patients with axSpA. The anonymous questionnaire included a series of items related to disease status (disease activity as measured by the BASDAI self-administered questionnaire, spinal stiffness, and functional limitation) and psychological aspects related to coping with the disease. All of the methodologies upon which the Atlas is based have been previously published in detail. This specific study includes data from 474 patients with recorded information about risk for mental disorders using the GHQ- 12. 7 / 19 Independent variables Disease activity Disease activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) with a range between 0 and 1010. In addition, spinal stiffness levels in the three areas of the vertebral column (cervical, dorsal, and lumbar) were collected, measured on a scale from lower to higher levels using an ordinal variable (1 = without limitation, 2 = mild limitation, 3 = moderate limitation, and 4 = severe limitation). Using this information, an index of spinal stiffness was created by adding, but without weighting, the degree of stiffness in each of the three areas. The resulting values ranged between 3 and 12. The Cronbach alpha value of this scale was 0.85, which attest to its consistency for assessing general stiffness. Function limitations in daily activities To determine the degree of functional limitation a composite index was employed, which included the sum of recorded limitation in 18 daily activities (dressing, grooming, bathing, tying shoelaces, moving about the home, walking up and down stairs, getting into/out of bed, using the toilet, shopping, preparing meals, eating, housework, walking, using public transportation, going to the doctor, driving, physical exercise, and sexual relations) using an ordinal variable (0 = none, 1 = little, 2 = some, and 3 = moderate). The resulting values oscillate between 0 and 54; thus, a value between 0 and 18 was set as a low limitation, that between 18 and 36 as a medium limitation, and that between 36 and 54 as an indication of high limitation. The Cronbach alpha value of this scale was 0.964, guaranteeing its reliability as a means for assessing limitation. 8 / 19 Sociodemographic aspects The following demographic aspects were also collected: gender, age, living as a couple, education level, employment status, and whether the individual belonged to a patient association. Comorbidity of mental health Finally, patients were queried about any previous mental health diagnosis (made by psychologist or psychiatrist), including anxiety or depression. Such diagnoses of depression and/or anxiety referred only to some point(s) in the past and patients were asked to provide a positive answer only when said diagnosis had been made by a psychologist/psychiatrist based on clinical criteria. Dependent variable Risk of mental disorder The risk of mental disorder (RMD) was determined by using the GHQ-1211, which consists of 12 items, each one assessing the severity of a mental health problems during the previous four weeks using a Likert scale (0-1-2-3). Thus, a maximum score of 36 was obtained; higher scores reflected an increased risk of psychiatric morbidity. However, to determine the risk of patients suffering with poor mental health, these scores were transferred to a GHQ scale, where 0 or 1 = 0, and 2 or 3 = 1. Following this methodology, the majority of studies found that scores equal to or greater than 3 indicated a high risk of poor mental health; therefore, we used this cut-off point for the present study12. The GHQ-12 offers reliability in studies developed within the Spanish population, resulting in a Cronbach's alpha that oscillated between 0.76 and 0.9011,13. In our study, a Cronbach's alpha of 0.934 was obtained, which supported the reliability hypothesis of this scale. 9 / 19 Statistical analysis The statistical analysis was conducted in three stages. The first step focused on the descriptive statistics for the sample and the study variables. The second step consisted of bivariate regression analyses of each predictor vis-à-vis the risk of poor mental health (GHQ-12) was performed. Here, nonparametric contrasts were made since the GHQ-12 values obtained did not follow a normal distribution pattern. For quantitative variables, Mann-Whitney tests for two categories and Kruskall-Wallis tests for more than two categories were performed. For categorical variables, chi square independence or Fisher tests were employed. In addition, the Spearman correlation coefficient was utilized to assess whether there was a relationship between mental health status (GHQ-12) and the different quantitative factors, such as the level of disease activity as measured by BASDAI. The third step evaluated the independent influence of disease outcomes on mental health by using a hierarchical multiple regression analysis with those that had shown a significant relationship with mental health status in the bivariate analyses conducted during the second step. For the hierarchical regression analysis, variables were grouped into three conceptual categories: (1) sociodemographic variables, (2) comorbidities, and (3) physical variables. This analysis introduced the variables of each category in a step-by-step fashion, thereby allowing for model comparison by building several regression models. Each model added variables to the previous one at each step; later models always included smaller models in their previous steps. In this case, our interest was to determine whether newly added conceptual categories of variables showed a significant improvement in R2 (the proportion of explained variance in GHQ-12 by the model). Finally, a stepwise forward regression multivariable analysis was carried out, which included the variables that passed an F test, in order to ascertain the best associated factors. 16 / 19 REFERENCES 1. Kiltz U, van der Heijde D. Health-related quality of life in patients with rheumatoid arthritis and in patients with ankylosing spondylitis. Clin Exp Rheumatol. 2009;27(Suppl 55):S108-11. 2. Lim HJ, Lim HS, Lee MS. Relationship between self-efficacy and exercise duration in patients with ankylosing spondylitis. Clin Rheumatol 2005;24:442-3. 3. Penhoat M, Saraux A, Le Goff B, Augereau P, Maugars Y, Berthelot JM. High pain catastrophizing scores in one-fourth of patients on biotherapy for spondylarthritis or rheumatoid arthritis. Jt Bone Spine 2014;81:235-9. 4. Yagiz A, Kokacya M, Copoglu U, et al. The effect of social support and severity of the disease on posttraumatic growth in ankylosing spondylitis. Acta Medica Mediterr 2014;30:1355-9. 5. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med 2000;160:2101-7. 6. Jang JH, Green CE, Assassi S, et al. The contribution of disease activity on functional limitations over time through psychological mediators: a 12-month longitudinal study in patients with ankylosing spondylitis. Rheumatology (Oxford) 2011;50:2087-92. 7. Kilic G, Kilic E, Ozgocmen S. Relationship between psychiatric status, self-reported outcome measures, and clinical parameters in axial spondyloarthritis. Medicine (Baltimore) 2014;93:e337. 8. Zhao S, Thong D, Miller N, et al. The prevalence of depression in axial spondyloarthritis and its association with disease activity: a systematic review and meta-analysis. Arthritis Res Ther 2018;20:140. 9. Garrido-Cumbrera M, Navarro-Compán V, Zarco P, et al. Atlas of Axial Spondyloarthritis in 17 / 19 Spain 2017: Study Design and Population. Reumatol Clin 2018;S1699-258X:30183-9. 10. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 1994;21:2286-91. 11. Golderberg D, Williams P. A user’s guide to the General Health Questionnaire. Windsor, UK: NFER-Nelson; 1988. 12. Rocha KB, Pérez K, Rodríguez-Sanz M, Borrell C, Obiols JE. Prevalencia de problemas de salud mental y su asociación con variables socioeconómicas, de trabajo y salud: resultados de la Encuesta Nacional de Salud de España. Psicothema 2010;22:389-95. 13. Sánchez-López M del P, Dresch V. The 12-Item General Health Questionnaire (GHQ-12): reliability, external validity and factor structure in the Spanish population. Psicothema 2008;20:839-43. 14. Chan CYY, Tsang HHL, Lau CS, Chung HY. Prevalence of depressive and anxiety disorders and validation of the Hospital Anxiety and Depression Scale as a screening tool in axial spondyloarthritis patients. Int J Rheum Dis 2017;20:317-25. 15. Gu Z, Xu X, Shen B, et al. Anxiety and depression correlate with disease and quality-of-life parameters in Chinese patients with ankylosing spondylitis. Patient Prefer Adherence 2016;10:879-85. 16. Baysal Ö, Durmuş B, Ersoy Y, et al. Relationship between psychological status and disease activity and quality of life in ankylosing spondylitis. Rheumatol Int 2011;31:795-800. 17. Brionez TF, Assassi S, Reveille JD, et al. Psychological correlates of self-reported functional limitation in patients with ankylosing spondylitis. Arthritis Res Ther 2009;11:R182. 18. Brionez TF, Assassi S, Reveille JD, et al. Psychological correlates of self-reported disease activity in ankylosing spondylitis. J Rheumatol. 2010;37:829-34. 18 / 19 19. Domínguez CJD, Ugalde PF, Vilchez DR, Carretero-Dios H, Estévez EC. Positive and negative affective states and disease activity in ankylosing spondylitis. Rheumatol Int 2015;35:519- 24. 20. Jiang Y, Yang M, Wu H, et al. The relationship between disease activity measured by the BASDAI and psychological status, stressful life events, and sleep quality in ankylosing spondylitis. Clin Rheumatol 2015;34:503-10. 21. Bagcivan G, Cinar FI, Cinar M, Oflaz F, Uzun S, Pay S. Living with pain in ankylosing spondylitis: a qualitative study. Contemp Nurse 2015;51:135-47. 22. Shen CC, Hu LY, Yang AC, Kuo BIT, Chiang YY, Tsai SJ. Risk of Psychiatric Disorders following Ankylosing Spondylitis: A Nationwide Population-based Retrospective Cohort Study. J Rheumatol 2016;43:625-31. 23. van Genderen S, Plasqui G, van der Heijde D, et al. Social Role Participation and Satisfaction With Life: A Study Among Patients With Ankylosing Spondylitis and Population Controls. Arthritis Care Res (Hoboken) 2018;70:600-7. 24. Montacer Kchir M, Mehdi Ghannouchi M, Hamdi W, et al. Impact of the ankylosing spondylitis on the professional activity. Jt Bone Spine 2009;76:378-82. 25. Betegnie A-L, Gauchet A, Lehmann A, et al. Why Do Patients with Chronic Inflammatory Rheumatic Diseases Discontinue Their Biologics? An Assessment of Patients’ Adherence Using a Self-report Questionnaire. J Rheumatol 2016;43:724-30. 26. Salaffi F, Carotti M, Gasparini S, Intorcia M, Grassi W. The health-related quality of life in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: a comparison with a selected sample of healthy people. Health Qual Life Outcomes. 2009;7:25. 27. Haywood KL, Garratt AM, Jordan KP, Healey EL, Packham JC. Evaluation of ankylosing spondylitis quality of life (EASi-QoL): reliability and validity of a new patient-reported 19 / 19 outcome measure. J Rheumatol 2010;37:2100-09. 28. Rau J, Ehlebracht-König I, Petermann F. Impact of a motivational intervention on coping with chronic pain: results of a controlled efficacy study. Schmerz 2008;22:575-8. 29. Geenen R, Newman S, Bossema ER, Vriezekolk JE, Boelen PA. Psychological interventions for patients with rheumatic diseases and anxiety or depression. Best Pract Res Clin Rheumatol 2012;26:305-319.