Abstract
Medication adherence is a crucial part in the management of rheumatic diseases, especially with many such patients requiring long-term medications. In this paper, we aim to systematically review the literature for the factors associated with medication adherence in the rheumatic patient population. We carried out a systematic literature search using PubMed®, PsychInfo® and Embase ® with relevant keywords and employed the PRISMA® criteria. We included English peer-reviewed articles that studied the factors affecting medication adherence in patients with rheumatic diseases, which were assessed by two independent reviewers. Hand searches were conducted and relevant factors were extracted and classified using the World Health Organization (WHO)’s five dimensions of medication adherence. A simple diagram was drawn to summarise the factors extracted. 1977 articles were identified and reviewed and 90 articles were found to be relevant. A total of 17 factors and 38 sub-factors were identified and categorized based on the WHO’s five dimensions of medication adherence. A hand model for medication adherence was developed to succinctly summarise these dimension to remind clinicians the importance of medication adherence in daily practice. We conducted a systematic review on the various factors including patient, therapy, condition, health system and socioeconomic-related factors that affected medication adherence in rheumatic patients. We found 17 factors and 38 sub-factors that affected medication adherence in this population. This systematic review can facilitate future focused research in unexplored dimensions.
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References
Greenstein B, Greenstein A (2007) Concise clinical pharmacology. Pharmaceutical Press, London, p 102
Brown M, Bussell J (2011) Medication adherence: WHO cares? Mayo Clin Proc 86(4):304–314
Sangha O (2000) Epidemiology of rheumatic diseases. Rheumatology 39(Suppl 2):3–12
Hoving JL, Lacaille D, Urquhart DM, Hannu TJ, Sluiter JK, Frings-Dresen MH (2014) Non-pharmacological interventions for preventing job loss in workers with inflammatory arthritis. The Cochrane database of systematic reviews. Cd010208
Smolen JS, Breedveld FC, Burmester GR et al (2016) Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis 75:3–15
Zomahoun HT, Guenette L, Gregoire JP et al (2016) Effectiveness of motivational interviewing interventions on medication adherence in adults with chronic diseases: a systematic review and meta-analysis. Int J Epidemiol 46(2):589–602
Krueger KP, Berger BA, Felkey B (2005) Medication adherence and persistence: a comprehensive review. Adv Ther 22:313–356
De Geest S, Sabate E (2003) Adherence to long-term therapies: evidence for action. Eur J Cardiovasc Nurs 2:323
Wabe N, Lee A, Wechalekar M, McWilliams L, Proudman S, Wiese M (2017) Adherence to combination DMARD therapy and treatment outcomes in rheumatoid arthritis: a longitudinal study of new and existing DMARD users. Rheumatol Int 6(37):897–904
de Achaval S, Suarez-Almazor ME (2010) Treatment adherence to disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and systemic lupus erythematosus. Int J Clin Rheumatol 5:313–326
Burkhart PV, Sabate E (2003) Adherence to long-term therapies: evidence for action. J Nurs Scholarsh 35:207
Bernatsky S, Ehrmann Feldman D (2008) Discontinuation of methotrexate therapy in older patients with newly diagnosed rheumatoid arthritis: analysis of administrative health databases in Québec, Canada. Drugs Aging 25:879–884
Brandstetter S, Hertig S, Loss J, Ehrenstein B, Apfelbacher C (2016) The lesser of two evils…’—views of persons with rheumatoid arthritis on medication adherence: a qualitative study. Psychol Health 31:675–692
Bruera S, Barbo AG, Lopez-Olivo MA (2016) Use of medication reminders in patients with rheumatoid arthritis. Rheumatol Int 36:1543–1548
Brus H, van de Laar M, Taal E, Rasker J, Wiegman O (1999) Determinants of compliance with medication in patients with rheumatoid arthritis: the importance of self-efficacy expectations. Patient Educ Couns 36:57–64
Bugni VM, Ozaki LS, Okamoto KY et al (2012) Factors associated with adherence to treatment in children and adolescents with chronic rheumatic diseases. J Pediatria 88:483–488
Choi JY, Cho SK, Choi CB et al (2014) The risk factors for nonadherence to anti-rheumatic treatment in patients with rheumatoid arthritis. Ann Rheumatic Dis 73(Suppl 2):913
Chu LH, Kawatakar AA (2012) Long term medication adherence of adalimumab and etanercept among rheumatoid arthritis patients in Kaiser Permanente Southern California. Value Health 15:A40
Dalbeth N, Petrie KJ, House M et al (2011) Illness perceptions in patients with gout and the relationship with progression of musculoskeletal disability. Arthritis Care Res 63:1605–1612
De Cuyper E, De Gucht V, Maes S, Van Camp Y, De Clerck LS (2016) Determinants of methotrexate adherence in rheumatoid arthritis patients. Clin Rheumatol 35:1335–1339
Denoeud L, Mazieres B, Payen-Champenois C, Ravaud P (2005) First line treatment of knee osteoarthritis in outpatients in France: adherence to the EULAR 2000 recommendations and factors influencing adherence. Ann Rheum Dis 64:70–74
Ekşioǧlu E, Çakir B, Gürçay E, Çakci A (2005) Factors affecting medical treatment compliance in one-year follow up of rheumatoid arthritis patients. J Rheumatol Med Rehabil 16:177–182
Elliott RA (2008) Poor adherence to medication in adults with rheumatoid arthritis: reasons and solutions. Dis Manag Health Outcomes 16:13–29
Gadallah MA, Boulos DN, Gebrel A, Dewedar S, Morisky DE (2015) Assessment of rheumatoid arthritis patients’ adherence to treatment. Am J Med Sci 349:151–156
Gross R, Graybill J, Wahezi D, Jordan NC, Putterman C, Blanco I (2014) Increased education is associated with decreased compliance in an urban multi-ethnic lupus cohort. J Clin Cell Immunol 5:215–230
Hromadkova L, Soukup T, Vlcek J (2015) Quality of life and drug compliance: their interrelationship in rheumatic patients. J Eval Clin Prac 21:919–924
Koneru S, Kocharla L, Higgins GC et al (2008) Adherence to medications in systemic lupus erythematosus. J Clin Rheumatol 14:195–201
Kumar K, Gordon C, Barry R, Shaw K, Horne R, Raza K (2011) ‘It’s like taking poison to kill poison but I have to get better’: a qualitative study of beliefs about medicines in Rheumatoid arthritis and Systemic lupus erythematosus patients of South Asian origin. Lupus 20:837–844
Kumar K, Raza K, Nightingale P et al (2015) Determinants of adherence to disease modifying anti-rheumatic drugs in White British and South Asian patients with rheumatoid arthritis: a cross sectional study. BMC Musculoskelet Disord 16:396
Li P, Blum MA, Von Feldt J, Hennessy S, Doshi JA (2010) Adherence, discontinuation, and switching of biologic therapies in medicaid enrollees with rheumatoid arthritis. Value Health 13:805–812
Loew L, Brosseau L, Kenny GP et al (2016) Factors influencing adherence among older people with osteoarthritis. Clin Rheumatol 35:2283–2291
Marchesoni A, Zaccara E, Gorla R et al (2009) TNF-alpha antagonist survival rate in a cohort of rheumatoid arthritis patients observed under conditions of standard clinical practice. Ann NY Acad Sci 1173:837–846
Morgan C, McBeth J, Cordingley L et al (2015) The influence of behavioural and psychological factors on medication adherence over time in rheumatoid arthritis patients: a study in the biologics era. Rheumatology 54:1780–1791
Müller R, Kallikorm R, Põlluste K, Lember M (2012) Compliance with treatment of rheumatoid arthritis. Rheumatol Int 32:3131–3135
Neame R, Hammond A (2005) Beliefs about medications: a questionnaire survey of people with rheumatoid arthritis. Rheumatology 44:762–767
Pascual-Ramos V, Contreras-Yanez I, Villa AR, Cabiedes J, Rull-Gabayet M (2009) Medication persistence over 2 years of follow-up in a cohort of early rheumatoid arthritis patients: associated factors and relationship with disease activity and with disability. Arthritis Res Ther 11:R26
Pasma A, van’t Spijker A, Hazes JM, Busschbach JJ, Luime JJ (2013) Factors associated with adherence to pharmaceutical treatment for rheumatoid arthritis patients: a systematic review. Semin Arthritis Rheum 43:18–28
Pavelka K, Forejtova S, Stolfa J et al (2009) Anti-TNF therapy of ankylosing spondylitis in clinical practice. Results from the Czech national registry ATTRA. Clin Exp Rheumatol 27:958–963
Salaffi F, Carotti M, Di Carlo M, Farah S, Gutierrez M (2015) Adherence to anti-tumor necrosis factor therapy administered subcutaneously and associated factors in patients with rheumatoid arthritis. J Clin Rheumatol 21:419–425
Tesher MS, Onel KB (2012) The clinical spectrum of juvenile idiopathic arthritis in a large urban population. Curr Rheumatol Rep 14:116–120
Tuncay R, Eksioglu E, Cakir B, Gurcay E, Cakci A (2007) Factors affecting drug treatment compliance in patients with rheumatoid arthritis. Rheumatol Int 27:743–746
van den Bemt BJ, van den Hoogen FH, Benraad B, Hekster YA, van Riel PL, van Lankveld W (2009) Adherence rates and associations with nonadherence in patients with rheumatoid arthritis using disease modifying antirheumatic drugs. J Rheumatol 36:2164–2170
Viller F, Guillemin F, Briancon S, Moum T, Suurmeijer T, van den Heuvel W (1999) Compliance to drug treatment of patients with rheumatoid arthritis: a 3 year longitudinal study. J Rheumatol 26:2114–2122
Wong M, Mulherin D (2007) The influence of medication beliefs and other psychosocial factors on early discontinuation of disease-modifying anti-rheumatic drugs. Musculoskelet Care 5:148–159
Zandman-Goddard G, Amital H, Shamrayevsky N, Raz R, Shalev V, Chodick G (2013) Rates of adherence and persistence with allopurinol therapy among gout patients in Israel. Rheumatology 52:1126–1131
Zwikker HE, van Dulmen S, den Broeder AA, van den Bemt BJ, van den Ende CH (2014) Perceived need to take medication is associated with medication non-adherence in patients with rheumatoid arthritis. Patient Preference Adherence 8:1635–1645
Agarwal S, Zaman T, Handa R (2009) Retention rates of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis. Singapore Med J 50:686–692
Bendtsen P, Bjurulf P, Trell E, Lindstrom F, Larsson JE (1994) Treatment perspectives in rheumatoid arthritis: a descriptive study in a Swedish healthcare district. PharmacoEconomics 5:399–407
De Cuyper E, De Gucht V, Maes S, Van Camp Y, De Clerck LS (2016) Determinants of methotrexate adherence in rheumatoid arthritis patients. Clin Rheumatol 35:1335–1339
Doddapaneni S, Shetty R, Sabih I, Maddali K, Khera K (2014) Assessment of medication adherence in rheumatoid arthritis patients in a tertiary care hospital. Value Health 17:A774
Kumar K, Raza K, Gill P, Greenfield S (2016) The impact of using musculoskeletal ultrasound imaging and other influencing factors on medication adherence in patients with rheumatoid arthritis: a qualitative study. Patient Preference Adherence 10:1091–1100
Mjaavatten MD, Radner H, Yoshida K et al (2014) Inconsistent treatment with disease-modifying antirheumatic drugs: a longitudinal data analysis. J Rheumatol 41:2370–2378
Chu LH, Kawatkar AA, Gabriel SE (2015) Medication adherence and attrition to biologic treatment in rheumatoid arthritis patients. Clin Ther 37(660–66):e8
de Thurah A, Norgaard M, Johansen MB, Stengaard-Pedersen K (2010) Methotrexate compliance among patients with rheumatoid arthritis: the influence of disease activity, disease duration, and co-morbidity in a 10-year longitudinal study. Scand J Rheumatol 39:197–205
Li LM, Tessier-Cloutier B, Wang Y et al (2013) Assessing process of care in rheumatoid arthritis at McGill University hospitals. J Clin Rheumatol 19:175–179
Rashid N, Coburn BW, Wu YL et al (2015) Modifiable factors associated with allopurinol adherence and outcomes among patients with gout in an integrated healthcare system. Journal Rheumatol 42:504–512
**a Y, Yin R, Fu T et al (2016) Treatment adherence to disease-modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis. Patient Preference Adherence 10:735–742
Bonafede M, Johnson BH, Tang DH, Shah N, Harrison DJ, Collier DH (2015) Etanercept-methotrexate combination therapy initiators have greater adherence and persistence than triple therapy initiators with rheumatoid arthritis. Arthritis Care Res 67:1656–1663
Contreras-Yanez I, Ponce De Leon S, Cabiedes J, Rull-Gabayet M, Pascual-Ramos V (2010) Inadequate therapy behavior is associated to disease flares in patients with rheumatoid arthritis who have achieved remission with disease-modifying antirheumatic drugs. Am J Med Sci 340:282–290
de Vlam K, Boone C, The Prove Study Group A (2015) Treatment adherence, efficacy, and safety of etanercept in patients with active psoriatic arthritis and peripheral involvement in Belgium for 66 months (PROVE study). Clin Exp Rheumatol 33:624–631
Drenkard C, Dunlop-Thomas C, Easley K, Bao G, Brady T, Lim SS (2012) Benefits of a self-management program in low-income African-American women with systemic lupus erythematosus: results of a pilot test. Lupus 21:1586–1593
Hetland ML, Christensen IJ, Tarp U et al (2010) Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registry. Arthritis Rheum 62:22–32
Kim G, Barner JC, Rascati K, Richards K (2016) Examining time to initiation of biologic disease-modifying antirheumatic drugs and medication adherence and persistence among texas medicaid recipients with rheumatoid arthritis. Clin Ther 38:646–654
Kristensen LE, Saxne T, Nilsson JA, Geborek P (2006) Impact of concomitant DMARD therapy on adherence to treatment with etanercept and infliximab in rheumatoid arthritis. Results from a six-year observational study in southern Sweden. Arthritis Res Ther 8:R174
Malaviya AP, Ostor AJ (2012) Drug adherence to biologic DMARDS with a special emphasis on the benefits of subcutaneous abatacept. Patient Preference Adherence 6:589–596
Wong PK (2016) Medication adherence in patients with rheumatoid arthritis: why do patients not take what we prescribe? Rheumatol Int 36:1535–1542
Prudente LR, Diniz Jde S, Ferreira TX et al (2016) Medication adherence in patients in treatment for rheumatoid arthritis and systemic lupus erythematosus in a university hospital in Brazil. Patient Preference Adherence 10:863–870
Aaltonen KJ, Turunen JH, Sokka T, Puolakka K, Valleala H (2016) A survey on the medication adherence to methotrexate among rheumatoid arthritis patients treated with self-administered biologic drugs. Clin Exp Rheumatol 34:694–697
Cabrera-Marroquin R, Contreras-Yanez I, Alcocer-Castillejos N, Pascual-Ramos V (2014) Major depressive episodes are associated with poor concordance with therapy in rheumatoid arthritis patients: the impact on disease outcomes. Clin Exp Rheumatol 32:904–913
Julian LJ, Yelin E, Yazdany J et al (2009) Depression, medication adherence, and service utilization in systemic lupus erythematosus. Arthritis Rheum 61:240–246
Abobului M, Berghea F, Vlad V et al (2015) Evaluation of adherence to anti-osteoporosis treatment from the socio-economic context. Journal of medicine and life 8:119–123 (spec issue)
Flower C, Hambleton I, Campbell M (2016) The effect of psychosocial and neuropsychiatric factors on medication adherence in a cohort of women with systemic lupus erythematosus. J Clin Rheumatol 22:411–417
Iudici M, Russo B, Mitidieri M, Cuomo G, Valentini G (2015) Glucocorticoids in systemic sclerosis: patients’ beliefs and treatment adherence. Scand J Rheumatol 44:229–237
Arshad N, Ahmad NM, Saeed MA, Khan S, Batool S, Farman S (2016) Adherence to Methotrexate therapy in Rheumatoid Arthritis. Pak J Med Sci 32:413–417
Broderick JE, Stone AA, Smyth JM, Kaell AT (2004) The feasibility and effectiveness of an expressive writing intervention for rheumatoid arthritis via home-based videotaped instructions. Ann Behav Med 27:50–59
Durcan L, Clarke WA, Magder LS, Petri M (2015) Hydroxychloroquine blood levels in systemic lupus erythematosus: clarifying dosing controversies and improving adherence. J Rheumatol 42:2092–2097
Geryk LL, Blalock S, DeVellis RF, Morella K, Carpenter DM (2016) Associations between patient characteristics and the amount of arthritis medication information patients receive. J Comm 21:1122–1130
Abdul-Sattar AB, Abou El Magd SA (2015) Determinants of medication non-adherence in Egyptian patients with systemic lupus erythematosus: Sharkia Governorate. Rheumatol Int 35:1045–1051
Pascual-Ramos V, Contreras-Yanez I (2013) Motivations for inadequate persistence with disease modifying anti-rheumatic drugs in early rheumatoid arthritis: the patient’s perspective. BMC Musculoskelet Disord 14:336
Bonafede M, Johnson BH, Princic N, Shah N, Harrison DJ (2015) Cost per patient-year in response using a claims-based algorithm for the 2 years following biologic initiation in patients with rheumatoid arthritis. J Med Econ 18:376–389
Nasser-Ghodsi N, Harrold LR (2015) Overcoming adherence issues and other barriers to optimal care in gout. Curr Opin Rheumatol 27:134–138
Solomon DH, Tonner C, Lu B et al (2014) Predictors of stop** and starting disease-modifying antirheumatic drugs for rheumatoid arthritis. Arthritis Care Res 66:1152–1158
Wan SW, He HG, Mak A et al (2016) Health-related quality of life and its predictors among patients with rheumatoid arthritis. Appl Nurs Res 30:176–183
Carter EE, Barr SG, Clarke AE (2016) The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol 12:605–620
Yap Angela Frances, Thiru Thirumoorthy Yu, Kwan Heng (2016) Medication adherence in the elderly. J Clin Gerontol Geriatrics 2016(10):1016
Yap Angela Frances, Thiru Thirumoorthy Yu, Kwan Heng (2015) Systematic review of the barriers affecting medication adherence in older adults. Geriatrics Gerontol Int 2015(10):1111
Goh XTW, Tan YB, Thirumoorthy T, Kwan YH (2016) A systematic review of factors that influence treatment adherence in paediatric oncology patients. J Clin Pharm Ther 42:1–7
Joplin S, van der Zwan R, Joshua F, Wong PKK (2015) Medication adherence in patients with rheumatoid arthritis: the effect of patient education, health literacy, and musculoskeletal ultrasound. Biomed Res Int 2015:150658
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Co-first authors: Hendra Goh, Yu Heng Kwan and Yi Seah.
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Goh, H., Kwan, Y.H., Seah, Y. et al. A systematic review of the barriers affecting medication adherence in patients with rheumatic diseases. Rheumatol Int 37, 1619–1628 (2017). https://doi.org/10.1007/s00296-017-3763-9
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DOI: https://doi.org/10.1007/s00296-017-3763-9